αvβ3 and α5β1 integrin-specific ligands: From tumor angiogenesis inhibitors to vascularization promoters in regenerative medicine? Biotechnol. Adv. (IF 10.597) Pub Date : 2017-11-15 Luís A. Rocha, David A. Learmonth, Rui A. Sousa, António J. Salgado
Integrins are cell adhesion receptors predominantly important during normal and tumor angiogenesis. A sequence present on several extracellular matrix proteins composed of Arg-Gly-Asp (RGD) has attracted attention due to its role in cell adhesion mediated by integrins. The development of ligands that can bind to integrins involved in tumor angiogenesis and brake disease progression has resulted in new investigational drug entities reaching the clinical trial phase in humans. The use of integrin-specific ligands can be useful for the vascularization of regenerative medicine constructs, which remains a major limitation for translation into clinical practice. In order to enhance vascularization, immobilization of integrin-specific RGD peptidomimetics within constructs is a recommended approach, due to their high specificity and selectivity towards certain desired integrins. This review endeavours to address the potential of peptidomimetic-coated biomaterials as vascular network promoters for regenerative medicine purposes. Clinical studies involving molecules tracking active integrins in cancer angiogenesis and reasons for their failure are also addressed.
Targeting ncRNAs by plant secondary metabolites: The ncRNAs game in the balance towards malignancy inhibition Biotechnol. Adv. (IF 10.597) Pub Date : 2017-11-10 Diana Gulei, Nikolay Mehterov, Seyed Mohammad Nabavi, Atanas Georgiev Atanasov, Ioana Berindan-Neagoe
The current trend of combining state of the art technologies with quondam treatments in order to overcome existing gaps in clinics determined an increased interest into polyphenols, common dietary phytochemicals, for the prevention and treatment of chronic diseases, especially cancer. The reemergence of polyphenols in the cancer field is sustained by transcriptomics technologies able to identify coding and non-coding genes and their related signaling pathways modulated by natural compounds. Identification of the structural correspondence between interacting molecules will allow the development of more targeted and informed therapeutic strategies for cancer management.
Engineering strategies for enhanced production of protein and bio-products in Pichia pastoris: A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-11-10 Zhiliang Yang, Zisheng Zhang
Pichia pastoris has been recognized as one of the most industrially important hosts for heterologous protein production. Despite its high protein productivity, the optimization of P. pastoris cultivation is still imperative due to strain- and product-specific challenges such as promoter strength, methanol utilization type and oxygen demand. To address the issues, strategies involving genetic and process engineering have been employed. Optimization of codon usage and gene dosage, as well as engineering of promoters, protein secretion pathways and methanol metabolic pathways have proved beneficial to innate protein expression levels. Large-scale production of proteins via high cell density fermentation additionally relies on the optimization of process parameters including methanol feed rate, induction temperature and specific growth rate. Recent progress related to the enhanced production of proteins in P. pastoris via various genetic engineering and cultivation strategies are reviewed. Insight into the regulation of the P. pastoris alcohol oxidase 1 (AOX1) promoter and the development of methanol-free systems are highlighted. Novel cultivation strategies such as mixed substrate feeding are discussed. Recent advances regarding substrate and product monitoring techniques are also summarized. Application of P. pastoris to the production of biodiesel and other value-added products via metabolic engineering are also reviewed. P. pastoris is becoming an indispensable platform through the use of these combined engineering strategies.
Biotechnological potential of novel glycoside hydrolase family 70 enzymes synthesizing α-glucans from starch and sucrose Biotechnol. Adv. (IF 10.597) Pub Date : 2017-11-10 Joana Gangoiti, Tjaard Pijning, Lubbert Dijkhuizen
Transglucosidases belonging to the glycoside hydrolase (GH) family 70 are promising enzymatic tools for the synthesis of α-glucans with defined structures from renewable sucrose and starch substrates. Depending on the GH70 enzyme specificity, α-glucans with different structures and physicochemical properties are produced, which have found diverse (potential) commercial applications, e.g. in food, health and as biomaterials. Originally, the GH70 family was established only for glucansucrase enzymes of lactic acid bacteria that catalyze the synthesis of α-glucan polymers from sucrose. In recent years, we have identified 3 novel subfamilies of GH70 enzymes (designated GtfB, GtfC and GtfD), inactive on sucrose but converting starch/maltodextrin substrates into novel α-glucans. These novel starch-acting enzymes considerably enlarge the panel of α-glucans that can be produced. They also represent very interesting evolutionary intermediates between sucrose-acting GH70 glucansucrases and starch-acting GH13 α-amylases. Here we provide an overview of the repertoire of GH70 enzymes currently available with focus on these novel starch-acting GH70 enzymes and their biotechnological potential. Moreover, we discuss key developments in the understanding of structure-function relationships of GH70 enzymes in the light of available three-dimensional structure structures, and the protein engineering strategies that were recently applied to expand their natural product specificities.
Amino acid misincorporation in recombinant proteins Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-26 H. Edward Wong, Chung-Jr Huang, Zhongqi Zhang
Proteins provide the molecular basis for cellular structure, catalytic activity, signal transduction, and molecular transport in biological systems. Recombinant protein expression is widely used to prepare and manufacture novel proteins that serve as the foundation of many biopharmaceutical products. However, protein translation bioprocesses are inherently prone to low-level errors. These sequence variants caused by amino acid misincorporation have been observed in both native and recombinant proteins. Protein sequence variants impact product quality, and their presence can be exacerbated through cellular stress, overexpression, and nutrient starvation. Therefore, the cell line selection process, which is used in the biopharmaceutical industry, is not only directed towards maximizing productivity, but also focuses on selecting clones which yield low sequence variant levels, thereby proactively avoiding potentially inauspicious patient safety and efficacy outcomes. Here, we summarize a number of hallmark studies aimed at understanding the mechanisms of amino acid misincorporation, as well as exacerbating factors, and mitigation strategies. We also describe key advances in analytical technologies in the identification and quantification of sequence variants, and some practical considerations when using LC-MS/MS for detecting sequence variants.
Next generation organoids for biomedical research and applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-19 Yan-Ru Lou, Alan W. Leung
Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that employ cell materials derived from fetal and adult tissues and pluripotent stem cell cultures. We focus on key studies that exploit the self-organizing property of embryonic progenitors and the role of designer matrices and cell-free scaffolds in assisting organoid formation. We further explore the relationship between adult stem cells, niche factors, and other current developments that aim to enhance robust organoid maturation. From these works, we propose a standardized pipeline for the development of future protocols that would help generate more physiologically relevant human organoids for various biomedical applications.
Potential and limitations of Klebsiella pneumoniae as a microbial cell factory utilizing glycerol as the carbon source Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-19 Vinod Kumar, Sunghoon Park
Klebsiella pneumoniae is a Gram-negative facultative anaerobe that metabolizes glycerol efficiently under both aerobic and anaerobic conditions. This microbe is considered an outstanding biocatalyst for transforming glycerol into a variety of value-added products. Crude glycerol is a cheap carbon source and can be converted by K. pneumoniae into useful compounds such as lactic acid, 3-hydroxypropionic acid, ethanol, 1,3-propanediol, 2,3-butanediol, and succinic acid. This review summarizes glycerol metabolism in K. pneumoniae and its potential as a microbial cell factory for the production of commercially important acids and alcohols. Although many challenges remain, K. pneumoniae is a promising workhorse when glycerol is used as the carbon source.
Improved strategies for electrochemical 1,4-NAD(P)H2 regeneration: A new era of bioreactors for industrial biocatalysis Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-10 Clifford S. Morrison, William B. Armiger, David R. Dodds, Jonathan S. Dordick, Mattheos A.G. Koffas
Industrial enzymatic reactions requiring 1,4-NAD(P)H2 to perform redox transformations often require convoluted coupled enzyme regeneration systems to regenerate 1,4-NAD(P)H2 from NAD(P) and recycle the cofactor for as many turnovers as possible. Renewed interest in recycling the cofactor via electrochemical means is motivated by the low cost of performing electrochemical reactions, easy monitoring of the reaction progress, and straightforward product recovery. However, electrochemical cofactor regeneration methods invariably produce adventitious reduced cofactor side products which result in unproductive loss of input NAD(P). We review various literature strategies for mitigating adventitious product formation by electrochemical cofactor regeneration systems, and offer insight as to how a successful electrochemical bioreactor system could be constructed to engineer efficient 1,4-NAD(P)H2-dependent enzyme reactions of interest to the industrial biocatalysis community.
Silk fibroin/hydroxyapatite composites for bone tissue engineering Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-07 Mehdi Farokhi, Fatemeh Mottaghitalab, Saeed Samani, Mohammad Ali Shokrgozar, Subhas C. Kundu, Rui L. Reis, Yousef Fattahi, David L. Kaplan
Silk fibroin (SF) is a natural fibrous polymer with strong potential for many biomedical applications. SF has attracted interest in the field of bone tissue engineering due to its extraordinary characteristics in terms of elasticity, flexibility, biocompatibility and biodegradability. However, low osteogenic capacity has limited applications for SF in the orthopedic arena unless suitably functionalized. Hydroxyapatite (HAp) is a well-established bioceramic with biocompatibility and appropriate for constructing orthopedic and dental substitutes. However, HAp ceramics tend to be brittle which can restrict applications in the repair of load-bearing tissues such as bones. Therefore, blending SF and HAp combines the useful properties of both materials as bone constructs for tissue engineering, the subject of this review.
Recent advances in polysaccharide bio-based flocculants Biotechnol. Adv. (IF 10.597) Pub Date : 2017-10-07 Hossein Salehizadeh, Ning Yan, Ramin Farnood
Natural polysaccharides, derived from biomass feedstocks, marine resources, and microorganisms, have been attracting considerable attention as benign and environmentally friendly substitutes for synthetic polymeric products. Besides many other applications, these biopolymers are rapidly emerging as viable alternatives to harmful synthetic flocculating agents for the removal of contaminants from water and wastewater. In recent years, a great deal of effort has been devoted to improve the production and performance of polysaccharide bio-based flocculants. In this review, current trends in preparation and chemical modification of polysaccharide bio-based flocculants and their flocculation performance are discussed. Aspects including mechanisms of flocculation, biosynthesis, classification, purification and characterization, chemical modification, the effect of physicochemical factors on flocculating activity, and recent applications of polysaccharide bio-based flocculants are summarized and presented.
Heterotrophic cultivation of microalgae for pigment production: A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-22 Jianjun Hu, Dillirani Nagarajan, Quanguo Zhang, Jo-Shu Chang, Duu-Jong Lee
Pigments (mainly carotenoids) are important nutraceuticals known for their potent anti-oxidant activities and have been used extensively as high end health supplements. Microalgae are the most promising sources of natural carotenoids and are devoid of the toxic effects associated with synthetic derivatives. Compared to photoautotrophic cultivation, heterotrophic cultivation of microalgae in well-controlled bioreactors for pigments production has attracted much attention for commercial applications due to overcoming the difficulties associated with the supply of CO2 and light, as well as avoiding the contamination problems and land requirements in open autotrophic culture systems. In this review, the heterotrophic metabolic potential of microalgae and their uses in pigment production are comprehensively described. Strategies to enhance pigment production under heterotrophic conditions are critically discussed and the challenges faced in heterotrophic pigment production with possible alternative solutions are presented.
Cofactor engineering for more efficient production of chemicals and biofuels Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-20 Meng Wang, Biqiang Chen, Yunming Fang, Tianwei Tan
Cofactors are involved in numerous intracellular reactions and critically influence redox balance and cellular metabolism. Cofactor engineering can support and promote the biocatalysis process, even help driving thermodynamically unfavorable reactions forwards. To achieve efficient production of chemicals and biofuels, cofactor engineering strategies such as altering cofactor supply or modifying reactants' cofactor preference have been developed to maintain redox balance. This review focuses primarily on the effects of cofactor engineering on carbon and energy metabolism. Coupling carbon metabolism with cofactor engineering can promote large-scale production, and even offer possibilities for producing new products or converting new materials.
Current advances of succinate biosynthesis in metabolically engineered Escherichia coli Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-20 Li-Wen Zhu, Ya-Jie Tang
As an important intermediate feedstock, succinate is termed as one of the 12 bio-based platform chemicals. To improve its fermentative production, various strategies have been developed, but challenges are still ahead for succinate biosynthesis to be cost-competitive. In this article, strategies for succinate production through metabolic engineering of Escherichia coli are critically reviewed, with a focus on engineering by-product formation and CO2 fixation, substrate utilization, reducing power balance, metabolic evolution and transcriptional regulation, which provide insights for the current state of succinate production and perspectives for further research for more efficient and economical production of bio-based succinate.
Learning from quantitative data to understand central carbon metabolism Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-18 Fumio Matsuda, Yoshihiro Toya, Hiroshi Shimizu
Quantitative analysis of metabolism has been used to identify driver reactions occurring during cancer development and bottleneck reactions in the metabolic engineering of microorganisms. In this review, we compare the advantages and disadvantages of various metabolic analysis methods. We emphasize that metabolic flux analysis based on material balance is a critical method for quantitative investigations into cell metabolism. The absolute determination of metabolite concentration appears to be essential for evaluating the thermodynamic state of metabolism. Obtaining a precise read-out of regulatory mechanisms from the snapshot data remains challenging due to our insufficient knowledge of the control of metabolism.
Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-13 Pedro A. Saa, Lars K. Nielsen
Kinetic models are critical to predict the dynamic behaviour of metabolic networks. Mechanistic kinetic models for large networks remain uncommon due to the difficulty of fitting their parameters. Recent modelling frameworks promise new ways to overcome this obstacle while retaining predictive capabilities. In this review, we present an overview of the relevant mathematical frameworks for kinetic formulation, construction and analysis. Starting with kinetic formalisms, we next review statistical methods for parameter inference, as well as recent computational frameworks applied to the construction and analysis of kinetic models. Finally, we discuss opportunities and limitations hindering the development of larger kinetic reconstructions.
Zika virus structural biology and progress in vaccine development Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-12 Hsiao-Han Lin, Bak-Sau Yip, Li-Min Huang, Suh-Chin Wu
The growing number of zika virus (ZIKV) infections plus a 20-fold increase in neonatal microcephaly in newborns in Brazil have raised alarms in many countries regarding the threat to pregnant women. Instances of microcephaly and central nervous system malformations continue to increase in ZIKV outbreak regions. ZIKV is a small enveloped positive-strand RNA virus belonging to the Flavivirus genus of the Flaviviridae family. High-resolution ZIKV structures recently identified by cryo-electron microscopy indicate that the overall ZIKV structure is similar to those of other flaviviruses. With its compact surface, ZIKV is more thermally stable than the dengue virus (DENV). ZIKV E proteins have a characteristic “herringbone” structure with a single glycosylation site. The ZIKV E protein, the major protein involved in receptor binding and fusion, is formed as a head-to-tail dimer on the surfaces of viral particles. The E monomer consists of three distinct domains: DI, DII, and DIII. The finger-like DII contains a fusion loop (FL) that is inserted into the host cell endosomal membrane during pH-dependent conformational changes that drive fusion. Quaternary E:E dimer epitopes located at the interaction site of prM and E dimers can be further divided into two dimer epitopes. To date, more than 50 ZIKV vaccine candidates are now in various stages of research and development. Candidate ZIKV vaccines that are currently in phase I/II clinical trials include inactivated whole viruses, recombinant measles viral vector-based vaccines, DNA and mRNA vaccines, and a mosquito salivary peptide vaccine. Stabilized forms of ZIKV E:E dimer proteins have been successfully obtained either by introducing additional inter-subunit disulfide bond(s) in DII or via the direct assembly of E:E dimer proteins by immobilization with monomeric E proteins. The VLP-based approach is another alternative method for presenting native E:E dimer antigens among the vaccine components. Several forms of ZIKV VLPs have been reported featuring the co-expression of the prM-E, prM-E-NS1, C-prM-E, and NS2B/NS3 viral genes in human cells. To minimize the effect of the cross-reactive ADE-facilitating antibodies between ZIKV and DENV, several novel mutations have been reported either in or near the FL of DII or DIII to dampen the production of cross-reactive antibodies. Future ZIKV vaccine design efforts should be focused on eliciting improved neutralizing antibodies with a reduced level of cross-reactivity to confer sterilizing immunity.
Taxonomy, ecology and biotechnological applications of thraustochytrids: A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-11 Loris Fossier Marchan, Kim J. Lee Chang, Peter D. Nichols, Wilfrid J. Mitchell, Jane L. Polglase, Tony Gutierrez
Thraustochytrids were first discovered in 1934, and since the 1960's they have been increasingly studied for their beneficial and deleterious effects. This review aims to provide an enhanced understanding of these protists with a particular emphasis on their taxonomy, ecology and biotechnology applications. Over the years, thraustochytrid taxonomy has improved with the development of modern molecular techniques and new biochemical markers, resulting in the isolation and description of new strains. In the present work, the taxonomic history of thraustochytrids is reviewed, while providing an up-to-date classification of these organisms. It also describes the various biomarkers that may be taken into consideration to support taxonomic characterization of the thraustochytrids, together with a review of traditional and modern techniques for their isolation and molecular identification. The originality of this review lies in linking taxonomy and ecology of the thraustochytrids and their biotechnological applications as producers of docosahexaenoic acid (DHA), carotenoids, exopolysaccharides and other compounds of interest. The paper provides a summary of these aspects while also highlighting some of the most important recent studies in this field, which include the diversity of polyunsaturated fatty acid metabolism in thraustochytrids, some novel strategies for biomass production and recovery of compounds of interest. Furthermore, a detailed overview is provided of the direct and current applications of thraustochytrid-derived compounds in the food, fuel, cosmetic, pharmaceutical, and aquaculture industries and of some of the commercial products available. This review is intended to be a source of information and references on the thraustochytrids for both experts and those who are new to this field.
Chassis and key enzymes engineering for monoterpenes production Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-06 Lu Zhang, Wen-Hai Xiao, Ying Wang, Ming-Dong Yao, Guo-Zhen Jiang, Bo-Xuan Zeng, Ruo-Si Zhang, Ying-Jin Yuan
Microbial production of monoterpenes is often limited by their cytotoxicity and in vivo conversion. Therefore, alleviating cytotoxicity and reducing conversion by chassis engineering are highly desirable. On the other hand, engineering key enzymes is also critical for improving monoterpenes production through facilitating the biosynthesis process. Here we critically review recent advances in cytotoxicity alleviation, reducing in vivo conversion, selecting geranyl diphosphate synthase and engineering monoterpene synthases. These achievements would lead to the development of superior chassis with improved tolerance to cytotoxicity and rationally tailored metabolites profiles to improve titer, yield and productivity for the production of monoterpenes by microbial cells.
Amino acids production focusing on fermentation technologies – A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-06 Martina D'Este, Merlin Alvarado-Morales, Irini Angelidaki
Amino acids are attractive and promising biochemicals with market capacity requirements constantly increasing. Their applicability ranges from animal feed additives, flavour enhancers and ingredients in cosmetic to specialty nutrients in pharmaceutical and medical fields.This review gives an overview of the processes applied for amino acids production and points out the main advantages and disadvantages of each.Due to the advances made in the genetic engineering techniques, the biotechnological processes, and in particular the fermentation with the aid of strains such as Corynebacterium glutamicum or Escherichia coli, play a significant role in the industrial production of amino acids. Despite the numerous advantages of the fermentative amino acids production, the process still needs significant improvements leading to increased productivity and reduction of the production costs.Although the production processes of amino acids have been extensively investigated in previous studies, a comprehensive overview of the developments in bioprocess technology has not been reported yet. This review states the importance of the fermentation process for industrial amino acids production, underlining the strengths and the weaknesses of the process. Moreover, the potential of innovative approaches utilizing macro and microalgae or bacteria are presented.
Weaving for heart valve tissue engineering Biotechnol. Adv. (IF 10.597) Pub Date : 2017-08-04 Albert Liberski, Nadia Ayad, Dorota Wojciechowska, Radoslaw Kot, Duy M.P. Vo, Dilibaier Aibibu, Gerald Hoffmann, Chokri Cherif, Katharina Grobelny-Mayer, Marek Snycerski, Helmut Goldmann
Weaving is a resourceful technology which offers a large selection of solutions that are readily adaptable for tissue engineering (TE) of artificial heart valves (HV). The different ways that the yarns are interlaced in this technique could be used to produce complex architectures, such as the three-layer architecture of the leaflets. Once the assembly is complete, growth of cells in the scaffold would occur in the orientation of the yarn, enabling the deposition of extra cellular matrixes proteins in an oriented manner. Weaving technology is a rapidly evolving field that, first, needs to be understood, and then explored by tissue engineers, so that it could be used to create efficient scaffolds. Similarly, the textile engineers need to gain a basic understanding of key structural and mechanical aspects of the heart valve. The aim of this review is to provide the platform for joining these two fields and to enable cooperative research efforts. Moreover, examples of woven medical products and patents as well as related publication are discussed in this review, nevertheless due to the large, and continuously growing volume of data, only the aspects strictly associated with HVTE lay in the scope of this paper.
Breaking the mirror: l-Amino acid deaminase, a novel stereoselective biocatalyst Biotechnol. Adv. (IF 10.597) Pub Date : 2017-08-03 Gianluca Molla, Roberta Melis, Loredano Pollegioni
Enantiomerically pure amino acids are of increasing interest for the fine chemical, agrochemicals and pharmaceutical industries. During past years l-amino acids have been produced from deracemization of dl-solution employing the stereoselective flavoenzyme d-amino acid oxidase. On the other hand, the isolation of corresponding d-isomer was hampered by the scarce availability of a suitable l-amino acid oxidase activity. On this side, l-amino acid deaminase (LAAD), only present in the Proteus bacteria, represents a suitable alternative. This FAD-containing enzyme catalyzes the deamination of l-amino acids to the corresponding α-keto acids and ammonia, with no hydrogen peroxide production (a potentially dangerous oxidizing species) since the electrons of the reduced cofactor are transferred to a membrane-bound cytochrome. Very recently the structure of LAAD has been solved: in addition to a FAD-binding domain and to a substrate-binding domain, it also possesses an N-terminal putative transmembrane α-helix (residues 8–27, not present in the crystallized protein variant) and a small α + β subdomain (50–67 amino acids long, named “insertion module”) strictly interconnected to the substrate binding domain. Structural comparison showed that LAAD resembles the structure of several soluble amino acid oxidases, such as l-proline dehydrogenase, glycine oxidase or sarcosine oxidase, while only a limited structural similarity with d- or l-amino acid oxidase is apparent. In this review, we present an overview of the structural and biochemical properties of known LAADs and describe the advances that have been made in their biotechnological application also taking advantage from improved variants generated by protein engineering studies.
Stay connected: Electrical conductivity of microbial aggregates Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-30 Cheng Li, Keaton Larson Lesnik, Hong Liu
The discovery of direct extracellular electron transfer offers an alternative to the traditional understanding of diffusional electron exchange via small molecules. The establishment of electronic connections between electron donors and acceptors in microbial communities is critical to electron transfer via electrical currents. These connections are facilitated through conductivity associated with various microbial aggregates. However, examination of conductivity in microbial samples is still in its relative infancy and conceptual models in terms of conductive mechanisms are still being developed and debated. The present review summarizes the fundamental understanding of electrical conductivity in microbial aggregates (e.g. biofilms, granules, consortia, and multicellular filaments) highlighting recent findings and key discoveries. A greater understanding of electrical conductivity in microbial aggregates could facilitate the survey for additional microbial communities that rely on direct extracellular electron transfer for survival, inform rational design towards the aggregates-based production of bioenergy/bioproducts, and inspire the construction of new synthetic conductive polymers.
Towards systems metabolic engineering in Pichia pastoris Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-29 Jan-Philipp Schwarzhans, Tobias Luttermann, Martina Geier, Jörn Kalinowski, Karl Friehs
Glycosaminoglycans from marine sources as therapeutic agents Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-21 Jesus Valcarcel, Ramon Novoa-Carballal, Ricardo I. Pérez-Martín, Rui L. Reis, José Antonio Vázquez
Valorisation of softwood bark through extraction of utilizable chemicals. A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-21 M. Jablonsky, J. Nosalova, A. Sladkova, A. Haz, F. Kreps, J. Valka, S. Miertus, V. Frecer, M. Ondrejovic, J. Sima, I. Surina
Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described. Finally, some challenges and perspectives on the production of chemicals from bark are discussed.
Insight into immunocytes infiltrations in polymorphous light eruption Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-17 Dongyun Lei, Wenjuan Wu, Li Yang, Yan Li, Jiaqi Feng, Lechun Lyu, Li He
Polymorphous light eruption (PLE) which is one of the most common photodermatoses has been demonstrated to be immune-mediated disorder. Resistance to UV-induced immunosuppression resulting from differential immune cells infiltration and cytokines secretion has been highlighted in the pathogenesis of PLE. In this study, we reviewed differential patterns of immune cells infiltrations and cytokines secretion that may contribute to PLE occurrence and development.
Bioelectrohydrogenesis and inhibition of methanogenic activity in microbial electrolysis cells - A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-12 Rengasamy Karthikeyan, Ka Yu Cheng, Ammaiyappan Selvam, Arpita Bose, Jonathan W.C. Wong
Microbial electrolysis cells (MECs) are a promising technology for biological hydrogen production. Compared to abiotic water electrolysis, a much lower electrical voltage (~ 0.2 V) is required for hydrogen production in MECs. It is also an attractive waste treatment technology as a variety of biodegradable substances can be used as the process feedstock. Underpinning this technology is a recently discovered bioelectrochemical pathway known as “bioelectrohydrogenesis”. However, little is known about the mechanism of this pathway, and numerous hurdles are yet to be addressed to maximize hydrogen yield and purity. Here, we review various aspects including reactor configurations, microorganisms, substrates, electrode materials, and inhibitors of methanogenesis in order to improve hydrogen generation in MECs.
Microalgal-bacterial aggregates: Applications and perspectives for wastewater treatment Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-08 Guillermo Quijano, Juan S. Arcila, Germán Buitrón
Spheroids as vascularization units: From angiogenesis research to tissue engineering applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-08 Matthias W. Laschke, Michael D. Menger
Multi-cellular spheroids mimic the complex three-dimensional environment of natural tissues. Accordingly, they are also used as vascularization units in angiogenesis research and regenerative medicine. Spheroid sprouting assays are versatile in vitro models for the analysis of molecular and cellular determinants of blood vessel development, including different endothelial cell phenotypes, pro- and anti-angiogenic factors as well as cell-matrix and cell-cell interactions. In tissue engineering, spheroids serve in vivo as paracrine stimulators of angiogenesis and building blocks for the generation of prevascularized microtissues and branched vascular trees in macrotissues. Rapid progress in the automatized high-throughput production of spheroids currently provides the conditions for a widespread use of these applications in future drug discovery and bioengineering of functional organ substitutes.
GH62 arabinofuranosidases: Structure, function and applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-06-29 Casper Wilkens, Susan Andersen, Claire Dumon, Jean-Guy Berrin, Birte Svensson
Motivated by industrial demands and ongoing scientific discoveries continuous efforts are made to identify and create improved biocatalysts dedicated to plant biomass conversion. α-1,2 and α-1,3 arabinofuranosyl specific α-l-arabinofuranosidases (EC 220.127.116.11) are debranching enzymes catalyzing hydrolytic release of α-l-arabinofuranosyl residues, which decorate xylan or arabinan backbones in lignocellulosic and pectin constituents of plant cell walls. The CAZy database classifies α-l-arabinofuranosidases in Glycoside Hydrolase (GH) families GH2, GH3, GH43, GH51, GH54 and GH62. Only GH62 contains exclusively α-l-arabinofuranosidases and these are of fungal and bacterial origin. Twenty-two GH62 enzymes out of 223 entries in the CAZy database have been characterized and very recently new knowledge was acquired with regard to crystal structures, substrate specificities, and phylogenetics, which overall provides novel insights into structure/function relationships of GH62. Overall GH62 α-l-arabinofuranosidases are believed to play important roles in nature by acting in synergy with several cell wall degrading enzymes and members of GH62 represent promising candidates for biotechnological improvements of biofuel production and in various biorefinery applications.
Channeling in native microbial pathways: Implications and challenges for metabolic engineering Biotechnol. Adv. (IF 10.597) Pub Date : 2017-06-13 Mary H. Abernathy, Lian He, Yinjie J. Tang
Intracellular enzymes can be organized into a variety of assemblies, shuttling intermediates from one active site to the next. Eukaryotic compartmentalization within mitochondria and peroxisomes and substrate tunneling within multi-enzyme complexes have been well recognized. Intriguingly, the central pathways in prokaryotes may also form extensive channels, including the heavily branched glycolysis pathway. In vivo channeling through cascade enzymes is difficult to directly measure, but can be inferred from in vitro tests, reaction thermodynamics, transport/reaction modeling, analysis of molecular diffusion and protein interactions, or steady state/dynamic isotopic labeling. Channeling presents challenges but also opportunities for metabolic engineering applications. It rigidifies fluxes in native pathways by trapping or excluding metabolites for bioconversions, causing substrate catabolite repressions or inferior efficiencies in engineered pathways. Channeling is an overlooked regulatory mechanism used to control flux responses under environmental/genetic perturbations. The heterogeneous distribution of intracellular enzymes also confounds kinetic modeling and multiple-omics analyses. Understanding the scope and mechanisms of channeling in central pathways may improve our interpretation of robust fluxomic topology throughout metabolic networks and lead to better design and engineering of heterologous pathways.
Oxidoreductases on their way to industrial biotransformations Biotechnol. Adv. (IF 10.597) Pub Date : 2017-06-15 Angel T. Martínez, Francisco J. Ruiz-Dueñas, Susana Camarero, Ana Serrano, Dolores Linde, Henrik Lund, Jesper Vind, Morten Tovborg, Owik M. Herold-Majumdar, Martin Hofrichter, Christiane Liers, René Ullrich, Katrin Scheibner, Giovanni Sannia, Alessandra Piscitelli, Cinzia Pezzella, Mehmet E. Sener, Sibel Kılıç, Miguel Alcalde
Fungi produce heme-containing peroxidases and peroxygenases, flavin-containing oxidases and dehydrogenases, and different copper-containing oxidoreductases involved in the biodegradation of lignin and other recalcitrant compounds. Heme peroxidases comprise the classical ligninolytic peroxidases and the new dye-decolorizing peroxidases, while heme peroxygenases belong to a still largely unexplored superfamily of heme-thiolate proteins. Nevertheless, basidiomycete unspecific peroxygenases have the highest biotechnological interest due to their ability to catalyze a variety of regio- and stereo-selective monooxygenation reactions with H2O2 as the source of oxygen and final electron acceptor. Flavo-oxidases are involved in both lignin and cellulose decay generating H2O2 that activates peroxidases and generates hydroxyl radical. The group of copper oxidoreductases also includes other H2O2 generating enzymes - copper-radical oxidases - together with classical laccases that are the oxidoreductases with the largest number of reported applications to date. However, the recently described lytic polysaccharide monooxygenases have attracted the highest attention among copper oxidoreductases, since they are capable of oxidatively breaking down crystalline cellulose, the disintegration of which is still a major bottleneck in lignocellulose biorefineries, along with lignin degradation. Interestingly, some flavin-containing dehydrogenases also play a key role in cellulose breakdown by directly/indirectly “fueling” electrons for polysaccharide monooxygenase activation. Many of the above oxidoreductases have been engineered, combining rational and computational design with directed evolution, to attain the selectivity, catalytic efficiency and stability properties required for their industrial utilization. Indeed, using ad hoc software and current computational capabilities, it is now possible to predict substrate access to the active site in biophysical simulations, and electron transfer efficiency in biochemical simulations, reducing in orders of magnitude the time of experimental work in oxidoreductase screening and engineering. What has been set out above is illustrated by a series of remarkable oxyfunctionalization and oxidation reactions developed in the frame of an intersectorial and multidisciplinary European RTD project. The optimized reactions include enzymatic synthesis of 1-naphthol, 25-hydroxyvitamin D3, drug metabolites, furandicarboxylic acid, indigo and other dyes, and conductive polyaniline, terminal oxygenation of alkanes, biomass delignification and lignin oxidation, among others. These successful case stories demonstrate the unexploited potential of oxidoreductases in medium and large-scale biotransformations.
Progress and biotechnological prospects in fish transgenesis Biotechnol. Adv. (IF 10.597) Pub Date : 2017-06-08 Fernanda M.P. Tonelli, Samyra M.S.N. Lacerda, Flávia C.P. Tonelli, Guilherme M.J. Costa, Luiz Renato de França, Rodrigo R. Resende
The history of transgenesis is marked by milestones such as the development of cellular transdifferentiation, recombinant DNA, genetic modification of target cells, and finally, the generation of simpler genetically modified organisms (e.g. bacteria and mice). The first transgenic fish was developed in 1984, and since then, continuing technological advancements to improve gene transfer have led to more rapid, accurate, and efficient generation of transgenic animals. Among the established methods are microinjection, electroporation, lipofection, viral vectors, and gene targeting. Here, we review the history of animal transgenesis, with an emphasis on fish, in conjunction with major developments in genetic engineering over the past few decades. Importantly, spermatogonial stem cell modification and transplantation are two common techniques capable of revolutionizing the generation of transgenic fish. Furthermore, we discuss recent progress and future biotechnological prospects of fish transgenesis, which has strong applications for the aquaculture industry. Indeed, some transgenic fish are already available in the current market, validating continued efforts to improve economically important species with biotechnological advancements.
Three-dimensional printing: technologies, applications, and limitations in neurosurgery Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-24 Josephine U. Pucci, Brandon R. Christophe, Jonathan A. Sisti, Edward S. Connolly
Three-dimensional (3D) printers are a developing technology penetrating a variety of markets, including the medical sector. Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics. With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well. Digital Imaging and Communication in Medicine (DICOM) can be translated into Stereolithography (STL) files, which are then read and methodically built by 3D Printers. Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients. Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research. In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, we outline the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery, their applications, and the limitations that need to be overcome if 3D printers are to become common practice in the neurosurgical field.
Biocompatibility of hydrogel-based scaffolds for tissue engineering applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-27 Sheva Naahidi, Mousa Jafari, Megan Logan, Yujie Wang, Yongfang Yuan, Hojae Bae, Brian Dixon, P. Chen
Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.
Molecular features of grass allergens and development of biotechnological approaches for allergy prevention Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-20 Deborah L. Devis, Janet M. Davies, Dabing Zhang
Allergic diseases are characterized by elevated allergen-specific IgE and excessive inflammatory cell responses. Among the reported plant allergens, grass pollen and grain allergens, derived from agriculturally important members of the Poaceae family such as rice, wheat and barley, are the most dominant and difficult to prevent. Although many allergen homologs have been predicted from species such as wheat and timothy grass, fundamental aspects such as the evolution and function of plant pollen allergens remain largely unclear. With the development of genetic engineering and genomics, more primary sequences, functions and structures of plant allergens have been uncovered, and molecular component-based allergen-specific immunotherapies are being developed. In this review, we aim to provide an update on (i) the distribution and importance of pollen and grain allergens of the Poaceae family, (ii) the origin and evolution, and functional aspects of plant pollen allergens, (iii) developments of allergen-specific immunotherapy for pollen allergy using biotechnology and (iv) development of less allergenic plants using gene engineering techniques. We also discuss future trends in revealing fundamental aspects of grass pollen allergens and possible biotechnological approaches to reduce the amount of pollen allergens in grasses.
Ubiquitous Chromatin-opening Elements (UCOEs): Applications in biomanufacturing and gene therapy Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-17 Jonathan J. Neville, Joe Orlando, Kimberly Mann, Bethany McCloskey, Michael N. Antoniou
Ubiquitous Chromatin-opening Elements (UCOEs) are defined by their ability to consistently confer stable, site of integration-independent transgene expression that is proportional to copy number, including from within regions of heterochromatin such as centromeres. UCOEs structurally consist of methylation-free CpG islands encompassing single or dual divergently-transcribed housekeeping gene promoters. Since their discovery in 1999, UCOEs and their sub-fragments have found applications in areas of biotechnology requiring stable, reproducible, and high levels of gene expression. This review recounts the discovery of UCOEs and examines their current and future applications in protein therapeutic biomanufacturing and gene therapy.
Bioengineering bacterial outer membrane vesicles as vaccine platform Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-15 Matthias J.H. Gerritzen, Dirk E. Martens, René H. Wijffels, Leo van der Pol, Michiel Stork
Harnessing self-assembled peptide nanoparticles in epitope vaccine design Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-15 Manica Negahdaripour, Nasim Golkar, Nasim Hajighahramani, Sedigheh Kianpour, Navid Nezafat, Younes Ghasemi
Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized.
Occurrence and biosynthesis of carotenoids in phytoplankton Biotechnol. Adv. (IF 10.597) Pub Date : 2017-05-13 Jim Junhui Huang, Shaoling Lin, Wenwen Xu, Peter Chi Keung Cheung
Naturally occurring carotenoids are important sources of antioxidants, anti-cancer compounds and anti-inflammatory agents and there is thus considerable market demand for their pharmaceutical applications. Carotenoids are widely distributed in marine and freshwater organisms including microalgae, phytoplankton, crustaceans and fish, as well as in terrestrial plants and birds. Recently, phytoplankton-derived carotenoids have received much attention due to their abundance, rapid rate of biosynthesis and unique composition. The carotenoids that accumulate in particular phytoplankton phyla are synthesized by specific enzymes and play unique physiological roles. This review focuses on studies related to the occurrence of carotenoids in different phytoplankton phyla and the molecular aspects of their biosynthesis. Recent biotechnological advances in the isolation and characterization of some representative carotenoid synthases in phytoplankton are also discussed.
Maltooligosaccharide-forming amylase: Characteristics, preparation, and application Biotechnol. Adv. (IF 10.597) Pub Date : 2017-04-27 Sihui Pan, Ning Ding, Junyan Ren, Zhengbiao Gu, Caiming Li, Yan Hong, Li Cheng, Tod P. Holler, Zhaofeng Li
As member of glycosyl hydrolase family 13, maltooligosaccharide-forming amylases (MFAses) are specific and interesting because of their capacity to hydrolyze starch into functional maltooligosaccharides, which are usually composed of 2–10 α-d-glucopyranosyl units linked by α-1,4 glycosidic linkages. MFAses have been extensively studied during recent decades, and have shown promise in various industrial applications. This review begins by introducing the potential uses of maltooligosaccharides. Then it describes the progress in the identification, assay, action pattern, structure, and modification of MFAses. The review continues with tips concerning the preparation of MFAses, which aim to improve MFAse production to meet the needs of industry. Finally, the industrial uses of MFAses are described, focusing on the production of maltooligosaccharides and application in the bread industry. Recent progress has demonstrated that the MFAses are poised to become important industrial catalysts.
Growth media in anaerobic fermentative processes: The underestimated potential of thermophilic fermentation and anaerobic digestion Biotechnol. Adv. (IF 10.597) Pub Date : 2017-09-01 A.T.W.M. Hendriks, J.B. van Lier, M.K. de Kreuk
Fermentation and anaerobic digestion of organic waste and wastewater is broadly studied and applied. Despite widely available results and data for these processes, comparison of the generated results in literature is difficult. Not only due to the used variety of process conditions, but also because of the many different growth media that are used. Composition of growth media can influence biogas production (rates) and lead to process instability during anaerobic digestion. To be able to compare results of the different studies reported, and to ensure nutrient limitation is not influencing observations ascribed to process dynamics and/or reaction kinetics, a standard protocol for creating a defined growth medium for anaerobic digestion and mixed culture fermentation is proposed. This paper explains the role(s) of the different macro- and micronutrients, as well as the choices for a growth medium formulation strategy. In addition, the differences in nutrient requirements between mesophilic and thermophilic systems are discussed as well as the importance of specific trace metals regarding specific conversion routes and the possible supplementary requirement of vitamins. The paper will also give some insight into the bio-availability and toxicity of trace metals. A remarkable finding is that mesophilic and thermophilic enzymes are quite comparable at their optimum temperatures. This has consequences for the trace metal requirements of thermophiles under certain conditions. Under non-limiting conditions, the trace metal requirement of thermophilic systems is about 3 times higher than for mesophilic systems.
In-vitro in-vivo correlation (IVIVC) in nanomedicine: Is protein corona the missing link? Biotechnol. Adv. (IF 10.597) Pub Date : 2017-08-26 Priyanka Jain, R.S. Pawar, R.S. Pandey, Jitender Madan, Sulakshna Pawar, P.K. Lakshmi, M.S. Sudheesh
One of the unmet challenges in nanotechnology is to understand and establish the relationship between physicochemical properties of nanoparticles (NPs) and its biological interactions (bio-nano interactions). However, we are still far from assessing the biofate of NPs in a clear and unquestionable manner. Recent developments in the area of bio-nano interface and the understanding of protein corona (PC) has brought new insight in predicting biological interactions of NPs. PC refers to the spontaneous formation of an adsorbed layer of biomolecules on the surface of NPs in a biological environment. PC formation involves the spatiotemporal interplay of an intricate network of biological, environmental and particle characteristics. NPs with its PC can be viewed as a biological entity, which interacts with cells and barriers in a biological system. Recent studies on the bio-nano interface have revealed biological signatures that participate in cellular and physiological bioprocesses and control the biofate and toxicity of NPs. The ability of in-vitro derived parameters to forecast in-vivo consequences by developing a mathematical model forms the basis of in-vitro in-vivo correlation (IVIVC). Understanding the effect of bio-nano interactions on the biological consequences of NPs at the cellular and physiological level can have a direct impact on the translation of future nanomedicines and can lead to the ultimate goal of developing a mathematical IVIVC model. The review summarizes the emerging paradigms in the field of bio-nano-interface which clearly suggests an urgent need to revisit existing protocols in nanotechnology for defining the physicochemical correlates of bio-nano interactions.
Covalent and non-covalent chemical engineering of actin for biotechnological applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-08-19 Saroj Kumar, Alf Mansson
The cytoskeletal filaments are self-assembled protein polymers with 8–25 nm diameters and up to several tens of micrometres length. They have a range of pivotal roles in eukaryotic cells, including transportation of intracellular cargoes (primarily microtubules with dynein and kinesin motors) and cell motility (primarily actin and myosin) where muscle contraction is one example. For two decades, the cytoskeletal filaments and their associated motor systems have been explored for nanotechnological applications including miniaturized sensor systems and lab-on-a-chip devices. Several developments have also revolved around possible exploitation of the filaments alone without their motor partners. Efforts to use the cytoskeletal filaments for applications often require chemical or genetic engineering of the filaments such as specific conjugation with fluorophores, antibodies, oligonucleotides or various macromolecular complexes e.g. nanoparticles. Similar conjugation methods are also instrumental for a range of fundamental biophysical studies. Here we review methods for non-covalent and covalent chemical modifications of actin filaments with focus on critical advantages and challenges of different methods as well as critical steps in the conjugation procedures. We also review potential uses of the engineered actin filaments in nanotechnological applications and in some key fundamental studies of actin and myosin function. Finally, we consider possible future lines of investigation that may be addressed by applying chemical conjugation of actin in new ways.
Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology Biotechnol. Adv. (IF 10.597) Pub Date : 2017-08-05 Pavel Dvořák, Pablo I. Nikel, Jiří Damborský, Víctor de Lorenzo
Elimination or mitigation of the toxic effects of chemical waste released to the environment by industrial and urban activities relies largely on the catalytic activities of microorganisms—specifically bacteria. Given their capacity to evolve rapidly, they have the biochemical power to tackle a large number of molecules mobilized from their geological repositories through human action (e.g., hydrocarbons, heavy metals) or generated through chemical synthesis (e.g., xenobiotic compounds). Whereas naturally occurring microbes already have considerable ability to remove many environmental pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow revisiting the same environmental pollution challenges through fresh and far more powerful approaches. The focus on contaminated sites and chemicals has been broadened by the phenomenal problems of anthropogenic emissions of greenhouse gases and the accumulation of plastic waste on a global scale. In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering workflow.
Enabling tools for high-throughput detection of metabolites: Metabolic engineering and directed evolution applications Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-16 Jyun-Liang Lin, James M. Wagner, Hal S. Alper
Within the Design-Build-Test Cycle for strain engineering, rapid product detection and selection strategies remain challenging and limit overall throughput. Here we summarize a wide variety of modalities that transduce chemical concentrations into easily measured absorbance, luminescence, and fluorescence signals. Specifically, we cover protein-based biosensors (including transcription factors), nucleic acid-based biosensors, coupled enzyme reactions, bioorthogonal chemistry, and fluorescent and chromogenic dyes and substrates as modalities for detection. We focus on the use of these methods for strain engineering and enzyme discovery and conclude with remarks on the current and future state of biosensor development for application in the metabolic engineering field.
Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches Biotechnol. Adv. (IF 10.597) Pub Date : 2017-07-08 Javad Sharifi-Rad, Bahare Salehi, Zorica Z. Stojanović-Radić, Patrick Valere Tsouh Fokou, Marzieh Sharifi-Rad, Gail B. Mahady, Majid Sharifi-Rad, Mohammad-Reza Masjedi, Temitope O. Lawal, Seyed Abdulmajid Ayatollahi, Javid Masjedi, Razieh Sharifi-Rad, William N. Setzer, Mehdi Sharifi-Rad, Farzad Kobarfard, Atta-ur Rahman, Muhammad Iqbal Choudhary, Athar Ata, Marcello Iriti
Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.
Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects Biotechnol. Adv. (IF 10.597) Pub Date : 2017-04-24 Naresh Kasoju, Hui Wang, Bo Zhang, Julian George, Shan Gao, James T. Triffitt, Zhanfeng Cui, Hua Ye
The plastic-adherent, fibroblast-like, clonogenic cells found in the human body now defined as multipotent “Mesenchymal Stromal Cells” (MSCs) hold immense potential for cell-based therapies. Recently, research and basic knowledge of these cells has fast-tracked, both from fundamental and translational perspectives. There have been important discoveries with respect to the available variety of tissue sources, the development of protocols for their easy isolation and in vitro expansion and for directed differentiation into various cell types. In addition, there has been discovery of novel abilities such as immune-modulation and further development of the use of biomaterials to aid isolation, expansion and differentiation together with improved delivery to the selected optimal tissue site. However, the molecular fingerprint of MSCs in these contexts remains imprecise and inadequate. Consequently, without this crucial knowledge it is difficult to achieve progress to determine with precision their practical developmental potentials. Detailed investigations on the global gene expression, or transcriptome, of MSCs could offer essential clues in this regard. In this article, we address the challenges associated with MSC transcriptome studies, the paradoxes observed in published experimental results and the need for careful transcriptomic analysis. We describe the exemplary applications with various transcriptome platforms that are used to address the variation in biomarkers and the identification of differentiation processes. The evolution and the potentials for adapting next-generation sequencing (NGS) technology in transcriptome analysis are discussed. Lastly, based on review of the existing understanding and published studies, we propose how NGS may be applied to promote further understanding of the biology of MSCs and their use in allied fields such as regenerative medicine.
Lactobacilli and pediococci as versatile cell factories – Evaluation of strain properties and genetic tools Biotechnol. Adv. (IF 10.597) Pub Date : 2017-04-07 Elleke F. Bosma, Jochen Forster, Alex Toftgaard Nielsen
This review discusses opportunities and bottlenecks for cell factory development of Lactic Acid Bacteria (LAB), with an emphasis on lactobacilli and pediococci, their metabolism and genetic tools. In order to enable economically feasible bio-based production of chemicals and fuels in a biorefinery, the choice of product, substrate and production organism is important. Currently, the most frequently used production hosts include Escherichia coli and Saccharomyces cerevisiae, but promising examples are available of alternative hosts such as LAB. Particularly lactobacilli and pediococci can offer benefits such as thermotolerance, an extended substrate range and increased tolerance to stresses such as low pH or high alcohol concentrations. This review will evaluate the properties and metabolism of these organisms, and provide an overview of their current biotechnological applications and metabolic engineering. We substantiate the review by including experimental results from screening various lactobacilli and pediococci for transformability, growth temperature range and ability to grow under biotechnologically relevant stress conditions. Since availability of efficient genetic engineering tools is a crucial prerequisite for industrial strain development, genetic tool development is extensively discussed. A range of genetic tools exist for Lactococcus lactis, but for other species of LAB like lactobacilli and pediococci such tools are less well developed. Whereas lactobacilli and pediococci have a long history of use in food and beverage fermentation, their use as platform organisms for production purposes is rather new. By harnessing their properties such as thermotolerance and stress resistance, and by using emerging high-throughput genetic tools, these organisms are very promising as versatile cell factories for biorefinery applications.
Application of single-cell technology in cancer research Biotechnol. Adv. (IF 10.597) Pub Date : 2017-04-05 Shao-Bo Liang, Li-Wu Fu
In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena. We believe that the clinical application of single-cell technology will be beneficial in cancer diagnostics and treatment, and ultimately improve survival in cancer patients.
Encapsulation systems for the delivery of hydrophilic nutraceuticals: Food application Biotechnol. Adv. (IF 10.597) Pub Date : 2017-04-01 N.P. Aditya, Yadira Gonzalez Espinosa, Ian T. Norton
Increased health risk associated with the sedentary life style is forcing the food manufacturers to look for food products with specific or general health benefits e.g. beverages enriched with nutraceuticals like catechin, curcumin rutin. Compounds like polyphenols, flavonoids, vitamins are the good choice of bioactive compounds that can be used to fortify the food products to enhance their functionality. However due to low stability and bioavailability of these bioactives (both hydrophobic and hydrophilic) within the heterogeneous food microstructure and in the Gastro Intestinal Tract (GIT), it becomes extremely difficult to pass on the real health benefits to the consumers.Recent developments in the application of nano-delivery systems for food product development is proving to be a game changer which has raised the expectations of the researchers, food manufacturers and consumers regarding possibility of enhancing the functionality of bioactives within the fortified food products. In this direction, nano/micro delivery systems using lipids, surfactants and other materials (carbohydrates, polymers, complexes, protein) have been fabricated to stabilize and enhance the biological activity of the bioactive compounds.In the present review, current status of the various delivery systems that are used for the delivery of hydrophilic bioactives and future prospects for using other delivery systems that have been not completely explored for the delivery of hydrophilic bioactives e.g. niosomes; bilosomes, cubosomes are discussed.
Very-large-scale production of antibodies in plants: The biologization of manufacturing Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-25 J.F. Buyel, R.M. Twyman, R. Fischer
Gene technology has facilitated the biologization of manufacturing, i.e. the use and production of complex biological molecules and systems at an industrial scale. Monoclonal antibodies (mAbs) are currently the major class of biopharmaceutical products, but they are typically used to treat specific diseases which individually have comparably low incidences. The therapeutic potential of mAbs could also be used for more prevalent diseases, but this would require a massive increase in production capacity that could not be met by traditional fermenter systems. Here we outline the potential of plants to be used for the very-large-scale (VLS) production of biopharmaceutical proteins such as mAbs. We discuss the potential market sizes and their corresponding production capacities. We then consider available process technologies and scale-down models and how these can be used to develop VLS processes. Finally, we discuss which adaptations will likely be required for VLS production, lessons learned from existing cell culture-based processes and the food industry, and practical requirements for the implementation of a VLS process.
Lignin-enzyme interaction: Mechanism, mitigation approach, modeling, and research prospects Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-25 Xiang Li, Yi Zheng
The adverse environmental impacts of the fossil fuel and the concerns of energy security necessitate the development of alternative clean energy sources from renewable feedstocks. Lignocellulosic biomass is a 2nd generation feedstock used in the production of biofuels and bio-based products that are conventionally derived from fossil resources. The biochemical conversion, which entails biomass pretreatment, enzymatic hydrolysis and fermentation, is one major platform used to transform lignocelluloses into biofuels. However, lignin presents many challenges to enzymatic hydrolysis leading to the need of high enzyme dose, low hydrolysis yield, low level of recyclability, high cost of enzymatic hydrolysis (because of the high cost of enzymes), and so on. Therefore, enzymatic hydrolysis, which is not cost effective, becomes one of major cost contributors. To mitigate the negative effects of lignin, extensive research has been conducted to explore the fundamental mechanisms of lignin-enzyme interactions to develop technologies to overcome the negative effects of lignin on enzymatic hydrolysis. Non-productive adsorption, which is characterized by hydrophobic, electrostatic and/or hydrogen bonding interactions, is widely known as the primary mechanism governing lignin-enzyme interactions. In addition, lignin-enzyme interaction is also influenced by steric hindrance (i.e., the physical blocking of enzyme access to carbohydrates by lignin). However, the mechanisms underlying the lignin-enzyme interactions remain unclear. This article aims to present a comprehensive review on the lignin-enzyme interactions (i.e. the mechanism, governing driving forces, modeling, and technologies for mitigating the negative effect of lignin). The current challenges inherent in this process and possible avenues of research in cellulosic biorefinery conclude this article.
Transport of bacteria in porous media and its enhancement by surfactants for bioaugmentation: A review Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-23 Hua Zhong, Guansheng Liu, Yongbing Jiang, Jinzhong Yang, Yang Liu, Xin Yang, Zhifeng Liu, Guangming Zeng
The success of bioaugmentation processes for groundwater bioremediation requires efficient transport of bacteria in the subsurface environment. In this paper, the factors that influence transport of bacterial cells in porous media are reviewed and the effects of surfactants on the transport are discussed. Movement of bacterial cells in porous media is a process driven by advection and hydrodynamic dispersion forces of fluids. Immobilization of bacterial cells takes place due to processes such as adsorption and straining. Blocking and ripening along with bacterial migration process decrease and increase the retention of cells in porous media, respectively. Physicochemical properties of the porous media, groundwater chemistry, and properties of the bacterial cells affect the transport behavior. Surfactants have the potential to modify bacterial surface properties for both bacterial cells and medium solids, and thus enhance bacterial transport.
Is there any crosstalk between the chemotaxis and virulence induction signaling in Agrobacterium tumefaciens? Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-23 Minliang Guo, Zhiwei Huang, Jing Yang
Agrobacterium tumefaciens, a soil-born phytopathogenic bacterium, is well known as a nature's engineer due to its ability to genetically transform the host by transferring a DNA fragment (called T-DNA) from its Ti plasmid to host-cell genome. To combat the harsh soil environment and seek the appropriate host, A. tumefaciens can sense and be attracted by a large number of chemical compounds released by wounded host. As a member of α-proteobacterium, A. tumefaciens has a chemotaxis system different from that found in Escherichia coli, since many chemoattractants for A. tumefaciens chemotaxis are virulence (vir) inducers. However, advances in the study of the chemotaxis paradigm, E. coli chemotaxis system, have provided enough information to analyze the A. tumefaciens chemotaxis. At low concentration, chemoattractants elicit A. tumefaciens chemotaxis and attract the species to the wound sites of the host. At high concentration, chemoattractants induce the expression of virulence genes and trigger T-DNA transfer. Recent studies on the VirA and ChvE of the vir-induction system provide some evidences to support the crosstalk between chemotaxis and vir-induction. This review compares the core components of chemotaxis signaling system of A. tumefaciens with those observed in other species, discusses the connection between chemotaxis and vir-induction in A. tumefaciens, and proposes a model depicting the signaling crosstalk between chemotaxis and vir-induction.
Brewing up a storm: The genomes of lager yeasts and how they evolved Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-08 Chandre Monerawela, Ursula Bond
Yeasts used in the production of lager beers belong to the species Saccharomyces pastorianus, an interspecies hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus. The hybridisation event happened approximately 500–600 years ago and therefore S. pastorianus may be considered as a newly evolving species. The happenstance of the hybridisation event created a novel species, with unique genetic characteristics, ideal for the fermentation of sugars to produce flavoursome beer. Lager yeast strains retain the chromosomes of both parental species and also have sets of novel hybrid chromosomes that arose by recombination between the homeologous parental chromosomes. The lager yeasts are subdivided into two groups (I and II) based on the S. cerevisiae: S. eubayanus gene content and the types and numbers of hybrid chromosomes. Recently, whole genome sequences for several Group I and II lager yeasts and for many S. cerevisiae and S. eubayanus isolates have become available. Here we review the available genome data and discuss the likely origins of the parental species that gave rise to S. pastorianus. We review the compiled data on the composition of the lager yeast genomes and consider several evolutionary models to account for the emergence of the two distinct types of lager yeasts.
Current advances on fermentative biobutanol production using third generation feedstock Biotechnol. Adv. (IF 10.597) Pub Date : 2017-06-01 Yue Wang, Shih-Hsin Ho, Hong-Wei Yen, Dillirani Nagarajan, Nan-Qi Ren, Shuangfei Li, Zhangli Hu, Duu-Jong Lee, Akihiko Kondo, Jo-Shu Chang
Biobutanol is gaining more attention as a potential alternative to ethanol, and the demand for fermentative biobutanol production has renewed interest. The main challenge faced in biobutanol production is the availability of feedstock. Using conventional agricultural biomass as feedstock is controversial and less efficient, while microalgae, the third generation feedstock, are considered promising feedstock for biobutanol production due to their high growth rate and high carbohydrates content. This review is primarily focused on biobutanol production by using carbohydrate-rich microalgal feedstock. Key technologies and challenges involved in producing butanol from microalgae are discussed in detail and future directions are also presented.
Computational tools for exploring sequence databases as a resource for antimicrobial peptides Biotechnol. Adv. (IF 10.597) Pub Date : 2017-02-12 W.F. Porto, A.S. Pires, O.L. Franco
Data mining has been recognized by many researchers as a hot topic in different areas. In the post-genomic era, the growing number of sequences deposited in databases has been the reason why these databases have become a resource for novel biological information. In recent years, the identification of antimicrobial peptides (AMPs) in databases has gained attention. The identification of unannotated AMPs has shed some light on the distribution and evolution of AMPs and, in some cases, indicated suitable candidates for developing novel antimicrobial agents. The data mining process has been performed mainly by local alignments and/or regular expressions. Nevertheless, for the identification of distant homologous sequences, other techniques such as antimicrobial activity prediction and molecular modelling are required. In this context, this review addresses the tools and techniques, and also their limitations, for mining AMPs from databases. These methods could be helpful not only for the development of novel AMPs, but also for other kinds of proteins, at a higher level of structural genomics. Moreover, solving the problem of unannotated proteins could bring immeasurable benefits to society, especially in the case of AMPs, which could be helpful for developing novel antimicrobial agents and combating resistant bacteria.
Nanocarriers for microRNA delivery in cancer medicine Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-08 I. Fernandez-Piñeiro, I. Badiola, A. Sanchez
The number of deaths caused by cancer is expected to increase partly due to the lack of selectivity and undesirable systemic effects of current treatments. Advances in the understanding of microRNA (miRNA) functions and the ideal properties of nanosystems have brought increasing attention to the application of nanomedicine to cancer therapy. This review covers the different miRNA therapeutic strategies and delivery challenges for its application in cancer medicine. Current trends in inorganic, polymeric and lipid nanocarrier development for miRNA replacement or inhibition are summarized. To achieve clinical success, in-depth knowledge of the effects of the promotion or inhibition of specific miRNAs is required. To establish the dose and the length of treatment, it will be necessary to study the duration of gene silencing. Additionally, efforts should be made to develop specifically targeted delivery systems to cancer cells to reduce doses and unwanted effects. In the near future, the combination of miRNAs with other therapeutic approaches is likely to play an important role in addressing the heterogeneity of cancer.
Pediococcus spp.: An important genus of lactic acid bacteria and pediocin producers Biotechnol. Adv. (IF 10.597) Pub Date : 2017-03-08 Maria Carolina W. Porto, Taís Mayumi Kuniyoshi, P.O.S. Azevedo, Michele Vitolo, R.P.S. Oliveira
Probiotics have gained increasing attention due to several health benefits related to the human digestive and immune systems. Pediococcus spp. are lactic acid bacteria (LAB) that are widely described as probiotics and characterized as coccus-shaped bacteria (arranged in tetrads), Gram-positive, non-motile, non-spore forming, catalase-negative, and facultative anaerobes. There are many Pediococcus strains that produce pediocin, an effective antilisterial bacteriocin. Pediocins are small, cationic molecules consisting of a conserved hydrophilic N-terminal portion containing the YGNGV motif and an amphiphilic or hydrophobic C-terminal variable portion. A number of studies have been developed with Pediococcus isolated from multiple biological niches to conduct fermentation processes for pediocin or Pediococcus cell production. This review gathers the most significant information about the cultivation, mode of action, and variability of bacteriocins produced by Pediococcus spp., emphasizing their applications in the areas of food and clinical practice. This updated panorama assists in delimiting the challenges that still need to be overcome for pediocin use to be approved for human consumption and the food industry.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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