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Dynamic control over feedback regulatory mechanisms improves NADPH flux and xylitol biosynthesis in engineered E. coli Metab. Eng. (IF 7.263) Pub Date : 2021-01-16 Shuai Li; Zhixia Ye; Eirik A. Moreb; Jennifer N. Hennigan; Daniel Baez Castellanos; Tian Yang; Michael D. Lynch
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Efficient production of oxidized terpenoids via engineering fusion proteins of terpene synthase and cytochrome P450 Metab. Eng. (IF 7.263) Pub Date : 2021-01-19 Xi Wang; Jose Henrique Pereira; Susan Tsutakawa; Xinyue Fang; Paul D. Adams; Aindrila Mukhopadhyay; Taek Soon Lee
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Metabolic engineering of E. coli for pyocyanin production Metab. Eng. (IF 7.263) Pub Date : 2021-01-14 Adilson José da Silva; Josivan de Souza Cunha; Teri Hreha; Kelli Cristina Micocci; Heloisa Sobreiro Selistre-de-Araujo; Blanca Barquera; Mattheos A.G. Koffas
Pyocyanin is a secondary metabolite from Pseudomonas aeruginosa that belongs to the class of phenazines, which are aromatic nitrogenous compounds with numerous biological functions. Besides its antifungal and antimicrobial activities, pyocyanin is a remarkable redox-active molecule with potential applications ranging from the pharma industry to the development of microbial fuel cells. Nevertheless
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Model reduction of genome-scale metabolic models as a basis for targeted kinetic models Metab. Eng. (IF 7.263) Pub Date : 2021-01-22 R.P. van Rosmalen; R.W. Smith; V.A.P. Martins dos Santos; C. Fleck; M. Suarez-Diez
Constraint-based, genome-scale metabolic models are an essential tool to guide metabolic engineering. However, they lack the detail and time dimension that kinetic models with enzyme dynamics offer. Model reduction can be used to bridge the gap between the two methods and allow for the integration of kinetic models into the Design-Built-Test-Learn cycle. Here we show that these reduced size models
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Rewiring the native methanol assimilation metabolism by incorporating the heterologous ribulose monophosphate cycle into Methylorubrum extorquens Metab. Eng. (IF 7.263) Pub Date : 2021-01-22 Xiao-Jie Yuan; Wen-Jing Chen; Zeng-Xin Ma; Qian-Qian Yuan; Min Zhang; Lian He; Xu-Hua Mo; Chong Zhang; Chang-Tai Zhang; Meng-Ying Wang; Xin-Hui Xing; Song Yang
Methanol is assimilated through the serine cycle to generate acetyl-CoA without carbon loss. However, a highly active serine cycle requires high consumption of reducing equivalents and ATP, thereby leading to the impaired efficiency of methanol conversion to reduced chemicals. In the present study, a genome-scale flux balance analysis (FBA) predicted that the introduction of the heterologous ribulose
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Enhancement of the flavone contents of Scutellaria baicalensis hairy roots via metabolic engineering using maize Lc and Arabidopsis PAP1 transcription factors Metab. Eng. (IF 7.263) Pub Date : 2021-01-21 Chang Ha Park; Hui Xu; Hyeon Ji Yeo; Ye Eun Park; Geum-Sook Hwang; Nam Il Park; Sang Un Park
Baicalin, baicalein, and wogonin are valuable natural flavonoid compounds produced by Scutellaria baicalensis. In this study, we showed that the maize transcription factor Lc can enhance the production of these three flavonoids in hairy root cultures of S. baicalensis by comprehensively upregulating flavonoid biosynthesis pathway genes (SbPAL1, SbC4H, and Sb4CL) and baicalein 7-O-glucuronosyltransferase
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Rapid and simultaneous screening of pathway designs and chassis organisms, applied to engineered living materials Metab. Eng. (IF 7.263) Pub Date : 2021-01-16 Dechuan Meng; Nikita Mukhitov; Dana Neitzey; Matthew Lucht; Damen D. Schaak; Christopher A. Voigt
Achieving a high product titer through pathway optimization often requires screening many combinations of enzymes and genetic parts. Typically, a library is screened in a single chassis that is a model or production organism. Here, we present a technique where the library is first introduced into B. subtilis XPORT, which has the ability to transfer the DNA to many Gram-positive species using an inducible
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Transportome-wide engineering of Saccharomyces cerevisiae Metab. Eng. (IF 7.263) Pub Date : 2021-01-16 Guokun Wang; Iben Møller-Hansen; Mahsa Babaei; Vasil D'Ambrosio; Hanne Bjerre Christensen; Behrooz Darbani; Michael Krogh Jensen; Irina Borodina
Synthetic biology enables the production of small molecules by recombinant microbes for pharma, food, and materials applications. The secretion of products reduces the cost of separation and purification, but it is challenging to engineer due to the limited understanding of the transporter proteins' functions. Here we describe a method for genome-wide transporter disruption that, in combination with
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Serial propagation in water-in-oil emulsions selects for Saccharomyces cerevisiae strains with a reduced cell size or an increased biomass yield on glucose Metab. Eng. (IF 7.263) Pub Date : 2021-01-05 Rinke Johanna van Tatenhove-Pel; Emile Zwering; Daan Floris Boreel; Martijn Falk; Johan Hendrik van Heerden; Mariah B.M.J. Kes; Cindy Iris Kranenburg; Dennis Botman; Bas Teusink; Herwig Bachmann
In S. cerevisiae and many other micro-organisms an increase in metabolic efficiency (i.e. ATP yield on carbon) is accompanied by a decrease in growth rate. From a fundamental point of view, studying these yield-rate trade-offs provides insight in for example microbial evolution and cellular regulation. From a biotechnological point of view, increasing the ATP yield on carbon might increase the yield
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Role of cyanobacterial phosphoketolase in energy regulation and glucose secretion under dark anaerobic and osmotic stress conditions Metab. Eng. (IF 7.263) Pub Date : 2020-12-14 Derrick Shih-Wei Chuang; James C. Liao
Primary metabolism in cyanobacteria is built on the Calvin-Benson-Bassham (CBB) cycle, oxidative pentose phosphate (OPP) pathway, Embden–Meyerhof–Parnas (EMP) pathway, and the tricarboxylic acid (TCA) cycle. Phosphoketolase (Xpk), commonly found in cyanobacteria, is an enzyme that is linked to all these pathways. However, little is known about its physiological role. Here, we show that most of the
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Automated engineering of synthetic metabolic pathways for efficient association to reaction rules.biomanufacturing Metab. Eng. (IF 7.263) Pub Date : 2020-12-13 Irene Otero-Muras; Pablo Carbonell
Metabolic engineering involves the engineering and optimization of processes from single-cell to fermentation in order to increase production of valuable chemicals for health, food, energy, materials and others. A systems approach to metabolic engineering has gained traction in recent years thanks to advances in strain engineering, leading to an accelerated scaling from rapid prototyping to industrial
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Recent advances in constraint and machine learning-based metabolic modeling by leveraging stoichiometric balances, thermodynamic feasibility and kinetic law formalisms Metab. Eng. (IF 7.263) Pub Date : 2020-12-10 Patrick F. Suthers; Charles J. Foster; Debolina Sarkar; Lin Wang; Costas D. Maranas
Understanding the governing principles behind organisms’ metabolism and growth underpins their effective deployment as bioproduction chassis. A central objective of metabolic modeling is predicting how metabolism and growth are affected by both external environmental factors and internal genotypic perturbations. The fundamental concepts of reaction stoichiometry, thermodynamics, and mass action kinetics
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CRISPR-derived genome editing technologies for metabolic engineering Metab. Eng. (IF 7.263) Pub Date : 2020-12-08 Keiji Nishida; Akihiko Kondo
In metabolic engineering, genome editing tools make it much easier to discover and evaluate relevant genes and pathways and construct strains. Clustered regularly interspaced palindromic repeats (CRISPR)-associated (Cas) systems now have become the first choice for genome engineering in many organisms includingindustrially relevant ones. Targeted DNA cleavage by CRISPR-Cas provides variousgenome engineering
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Combinatorial metabolic pathway assembly approaches and toolkits for modular assembly Metab. Eng. (IF 7.263) Pub Date : 2020-12-07 Rosanna Young; Matthew Haines; Marko Storch; Paul S. Freemont
Synthetic Biology is a rapidly growing interdisciplinary field that is primarily built upon foundational advances in molecular biology combined with engineering design principles such as modularity and interoperability. The field considers living systems as programmable at the genetic level and has been defined by the development of new platform technologies and methodological advances. A key concept
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Energy coupling of membrane transport and efficiency of sucrose dissimilation in yeast Metab. Eng. (IF 7.263) Pub Date : 2020-12-03 Ryan K. Henderson; Sophie C. de Valk; Bert Poolman; Robert Mans
Proton coupled transport of α-glucosides via Mal11 into Saccharomyces cerevisiae costs one ATP per imported molecule. Targeted mutation of all three acidic residues in the active site resulted in sugar uniport, but expression of these mutant transporters in yeast did not enable growth on sucrose. We then isolated six unique transporter variants of these mutants by directed evolution of yeast for growth
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Constructing an ethanol utilization pathway in Escherichia coli to produce acetyl-CoA derived compounds Metab. Eng. (IF 7.263) Pub Date : 2020-11-25 Hong Liang; Xiaoqiang Ma; Wenbo Ning; Yurou Liu; Anthony J. Sinskey; Gregory Stephanopoulos; Kang Zhou
Engineering microbes to utilize non-conventional substrates could create short and efficient pathways to convert substrate into product. In this study, we designed and constructed a two-step heterologous ethanol utilization pathway (EUP) in Escherichia coli by using acetaldehyde dehydrogenase (encoded by ada) from Dickeya zeae and alcohol dehydrogenase (encoded by adh2) from Saccharomyces cerevisiae
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Short and long-read ultra-deep profiles emerging heterogeneity across five platform Escherichia coli strains Metab. Eng. (IF 7.263) Pub Date : 2020-11-24 Peter Rugbjerg; Anne Sofie Brask Dyerberg; Scott Quainoo; Christian Munck; Morten Otto Alexander Sommer
Reprogramming organisms for large-scale bioproduction counters their evolutionary objectives of fast growth and often leads to mutational collapse of the engineered production pathways during cultivation. Yet, the mutational susceptibility of academic and industrial Escherichia coli bioproduction host strains are poorly understood. In this study, we apply 2nd and 3rd generation deep sequencing to profile
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Regulatory molecule cAMP changes cell fitness of the engineered Escherichia coli for terpenoids production Metab. Eng. (IF 7.263) Pub Date : 2020-11-24 Seong-Hee Jeong; Ji-Bin Park; Yan Wang; Gye-Hwan Kim; Gaochuan Zhang; Gongyuan Wei; Chonglong Wang; Seon-Won Kim
Terpenoids are a class of natural compounds with many important functions and applications. They are synthesized from a long synthetic pathway of isoprenyl unit coupling with the myriads of terpene synthases. Owing to the catalytic divergence of terpenoids synthesis, microbial production of terpenoids is compromised to the complexity of pathway engineering and suffers from the metabolic engineering
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Metabolic engineering of tomato fruit enriched in L-DOPA Metab. Eng. (IF 7.263) Pub Date : 2020-11-23 Dario Breitel; Paul Brett; Saleh Alseekh; Alisdair R. Fernie; Eugenio Butelli; Cathie Martin
L-DOPA, also known as Levodopa or L-3,4-dihydroxyphenylalanine, is a non-standard amino acid, and the gold standard drug for the treatment for Parkinson's Disease (PD). Recently, a gene encoding the enzyme that is responsible for its synthesis, as a precursor of the coloured pigment group betalains, was identified in beetroot, BvCYP76AD6. We have engineered tomato fruit enriched in L-DOPA through overexpression
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Protocatechuate overproduction by Corynebacterium glutamicum via simultaneous engineering of native and heterologous biosynthetic pathways Metab. Eng. (IF 7.263) Pub Date : 2020-11-22 Takahisa Kogure; Masako Suda; Kazumi Hiraga; Masayuki Inui
Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is a natural bioactive phenolic acid potentially valuable as a pharmaceutical raw material owing to its diverse pharmacological activities. Corynebacterium glutamicum forms PCA as a key intermediate in a native pathway to assimilate shikimate/quinate through direct conversion of the shikimate pathway intermediate 3-dehydroshikimate (DHS), which
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Machine learning for metabolic engineering: A review Metab. Eng. (IF 7.263) Pub Date : 2020-11-19 Chris Lawson; Jose Manuel Martí; Tijana Radivojevic; Sai Vamshi R. Jonnalagadda; Reinhard Gentz; Nathan J. Hillson; Sean Peisert; Joonhoon Kim; Blake A. Simmons; Christopher J. Petzold; Steven W. Singer; Aindrila Mukhopadhyay; Deepti Tanjore; Josh Dunn; Hector Garcia Martin
Machine learning provides researchers a unique opportunity to make metabolic engineering more predictable. In this review, we offer an introduction to this discipline in terms that are relatable to metabolic engineers, as well as providing in-depth illustrative examples leveraging omics data and improving production. We also include practical advice for the practitioner in terms of data management
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Metabolic design for selective production of nicotinamide mononucleotide from glucose and nicotinamide Metab. Eng. (IF 7.263) Pub Date : 2020-11-18 Shinichiro Shoji; Taiki Yamaji; Harumi Makino; Jun Ishii; Akihiko Kondo
β-Nicotinamide mononucleotide (NMN) is, one of the nucleotide compounds, a precursor of NAD+ and has recently attracted attention as a nutraceutical. Here, we develop a whole-cell biocatalyst using Escherichia coli, which enabled selective and effective high production of NMN from the inexpensive feedstock substrates glucose and nicotinamide (Nam). Notably, we identify two actively functional transporters
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The heterologous production of terpenes by the thermophile Parageobacillus thermoglucosidasius in a consolidated bioprocess using waste bread Metab. Eng. (IF 7.263) Pub Date : 2020-11-13 Matthew Q. Styles; Edward A. Nesbitt; Timothy D. Hoffmann; Junichi Queen; Maria V. Ortenzi; David J. Leak
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NetRed, an algorithm to reduce genome-scale metabolic networks and facilitate the analysis of flux predictions Metab. Eng. (IF 7.263) Pub Date : 2020-11-06 Daniel J. Lugar; Sean G. Mack; Ganesh Sriram
Flux balance analysis (FBA) of large, genome-scale stoichiometric models (GSMs) is a powerful and popular method to predict cell-wide metabolic activity. FBA typically generates a flux vector containing O(1,000) fluxes. The interpretation of such a flux vector is difficult, even for expert users, because of the large size and complex topology of the underlying metabolic network. This interpretation
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Control of IgG glycosylation in CHO cell perfusion cultures by GReBA mathematical model supported by a novel targeted feed, TAFE Metab. Eng. (IF 7.263) Pub Date : 2020-11-05 Liang Zhang; Hubert Schwarz; MingLiang Wang; Andreas Castan; Håkan Hjalmarsson; Veronique Chotteau
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Engineering Yarrowia lipolytica for the selective and high-level production of isocitric acid through manipulation of mitochondrial dicarboxylate–tricarboxylate carriers Metab. Eng. (IF 7.263) Pub Date : 2020-11-05 Evgeniya Y. Yuzbasheva; Pasquale Scarcia; Tigran V. Yuzbashev; Eugenia Messina; Iuliia M. Kosikhina; Luigi Palmieri; Artem V. Shutov; Maria O. Taratynova; Rodrigo Ledesma Amaro; Ferdinando Palmieri; Sergey P. Sineoky; Gennaro Agrimi
During cultivation under nitrogen starvation, Yarrowia lipolytica produces a mixture of citric acid and isocitric acid whose ratio is mainly determined by the carbon source used. We report that mitochondrial succinate–fumarate carrier YlSfc1 controls isocitric acid efflux from mitochondria. YlSfc1 purified and reconstituted into liposomes transports succinate, fumarate, oxaloacetate, isocitrate and
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A guide to metabolic flux analysis in metabolic engineering: Methods, tools and applications Metab. Eng. (IF 7.263) Pub Date : 2020-11-04 Maciek R. Antoniewicz
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CRISPR-based metabolic pathway engineering Metab. Eng. (IF 7.263) Pub Date : 2020-11-02 Dongdong Zhao; Xinna Zhu; Hang zhou; Naxin Sun; Ting Wang; Changhao Bi; Xueli Zhang
A highly effective metabolic pathway is the key for an efficient cell factory. However, the engineered homologous or heterologous multi-gene pathway may be unbalanced, inefficient and causing the accumulation of potentially toxic intermediates. Therefore, pathways must be constructed optimally to minimize these negative effects and maximize catalytic efficiency. With the development of CRISPR technology
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Production of moth sex pheromones for pest control by yeast fermentation Metab. Eng. (IF 7.263) Pub Date : 2020-10-09 Carina Holkenbrink; Bao-Jian Ding; Hong-Lei Wang; Marie Inger Dam; Karolis Petkevicius; Kanchana Rueksomtawin Kildegaard; Leonie Wenning; Christina Sinkwitz; Bettina Lorántfy; Eleni Koutsoumpeli; Lucas França; Marina Pires; Carmem Bernardi; William Urrutia; Agenor Mafra-Neto; Bruno Sommer Ferreira; Dimitris Raptopoulos; Maria Konstantopoulou; Irina Borodina
The use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations. Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting
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Enhanced 2′-Fucosyllactose production by engineered Saccharomyces cerevisiae using xylose as a co-substrate Metab. Eng. (IF 7.263) Pub Date : 2020-10-22 Jae Won Lee; Suryang Kwak; Jing-Jing Liu; Sora Yu; Eun Ju Yun; Dong Hyun Kim; Cassie Liu; Kyoung Heon Kim; Yong-Su Jin
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Metabolic engineering of Escherichia coli for the production of benzoic acid from glucose Metab. Eng. (IF 7.263) Pub Date : 2020-10-14 Zi Wei Luo; Sang Yup Lee
Benzoic acid (BA) is an important platform aromatic compound in chemical industry and is widely used as food preservatives in its salt forms. Yet, current manufacture of BA is dependent on petrochemical processes under harsh conditions. Here we report the de novo production of BA from glucose using metabolically engineered Escherichia coli strains harboring a plant-like β-oxidation pathway or a newly
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Synthetic reconstruction of extreme high hydrostatic pressure resistance in Escherichia coli Metab. Eng. (IF 7.263) Pub Date : 2020-09-24 Elisa Gayán; Bram Van den Bergh; Jan Michiels; Chris W. Michiels; Abram Aertsen
Although high hydrostatic pressure (HHP) is an interesting parameter to be applied in bioprocessing, its potential is currently limited by the lack of bacterial chassis capable of surviving and maintaining homeostasis under pressure. While several efforts have been made to genetically engineer microorganisms able to grow at sublethal pressures, there is little information for designing backgrounds
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High-throughput screening for high-efficiency small-molecule biosynthesis Metab. Eng. (IF 7.263) Pub Date : 2020-10-02 Matthew Rienzo; Shaina J. Jackson; Lawrence K. Chao; Timothy Leaf; Thomas J. Schmidt; Adam H. Navidi; Dana C. Nadler; Maud Ohler; Michael D. Leavell
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Gene amplification, laboratory evolution, and biosensor screening reveal MucK as a terephthalic acid transporter in Acinetobacter baylyi ADP1 Metab. Eng. (IF 7.263) Pub Date : 2020-10-01 Isabel Pardo; Ramesh K. Jha; Ryan E. Bermel; Felicia Bratti; Molly Gaddis; Emily McIntyre; William Michener; Ellen L. Neidle; Taraka Dale; Gregg T. Beckham; Christopher W. Johnson
Microbial terephthalic acid (TPA) catabolic pathways are conserved among the few bacteria known to turnover this xenobiotic aromatic compound. However, to date there are few reported cases in which this pathway has been successfully expressed in heterologous hosts to impart efficient utilization of TPA as a sole carbon source. In this work, we aimed to engineer TPA conversion in Acinetobacter baylyi
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Engineering of Synechococcus sp. strain PCC 7002 for the photoautotrophic production of light-sensitive riboflavin (vitamin B2) Metab. Eng. (IF 7.263) Pub Date : 2020-09-28 Benjamin Kachel; Matthias Mack
Due to their capability of photosynthesis and autotrophic growth, cyanobacteria are currently investigated with regard to the sustainable production of a wide variety of chemicals. So far, however, no attempt has been undertaken to engineer cyanobacteria for the biotechnological production of vitamins, which is probably due to the light-sensitivity of many of these compounds. We now describe a photoautotrophic
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Adaptive laboratory evolution of Escherichia coli lacking cellular byproduct formation for enhanced acetate utilization through compensatory ATP consumption. Metab. Eng. (IF 7.263) Pub Date : 2020-09-12 Wonjae Seong,Gui Hwan Han,Hyun Seung Lim,Ji In Baek,Soo-Jung Kim,Donghyuk Kim,Seong Keun Kim,Hyewon Lee,Haseong Kim,Seung-Goo Lee,Dae-Hee Lee
Acetate has attracted great attention as a carbon source to develop economically feasible bioprocesses for sustainable bioproducts. Acetate is a less-preferred carbon source and a well-known growth inhibitor of Escherichia coli. In this study, we carried out adaptive laboratory evolution of an E. coli strain lacking four genes (adhE, pta, ldhA, and frdA) involved in acetyl-CoA consumption, allowing
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Single-gene regulated non-spore-forming Bacillus subtilis: Construction, transcriptome responses and applications for producing enzymes and surfactin. Metab. Eng. (IF 7.263) Pub Date : 2020-08-21 Miaomiao Wang,Huimin Yu,Xu Li,Zhongyao Shen
Bacillus subtilis, a spore-forming industrial bacterium, is widely used for production of enzymes and valuable chemicals. The spore-formation, however, always results in remarkably reduced cell-density, thereby reducing product yield. Here, we constructed different non-spore-forming B. subtilis mutants via single-gene regulation. During the three spore-forming stages: signal sensing, transduction,
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Engineering Corynebacterium glutamicum with a comprehensive genomic library and phage-based vectors. Metab. Eng. (IF 7.263) Pub Date : 2020-08-20 Filipe Marques,Andriy Luzhetskyy,Marta V Mendes
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Valorization of CO2 through lithoautotrophic production of sustainable chemicals in Cupriavidus necator. Metab. Eng. (IF 7.263) Pub Date : 2020-09-19 Shannon N Nangle,Marika Ziesack,Sarabeth Buckley,Disha Trivedi,Daniel M Loh,Daniel G Nocera,Pamela A Silver
Coupling recent advancements in genetic engineering of diverse microbes and gas-driven fermentation provides a path towards sustainable commodity chemical production. Cupriavidus necator H16 is a suitable species for this task because it effectively utilizes H2 and CO2 and is genetically tractable. Here, we demonstrate the versatility of C. necator for chemical production by engineering it to produce
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High-yield production of L-valine in engineered Escherichia coli by a novel two-stage fermentation. Metab. Eng. (IF 7.263) Pub Date : 2020-09-19 Yanan Hao,Qian Ma,Xiaoqian Liu,Xiaoguang Fan,Jiaxuan Men,Heyun Wu,Shuai Jiang,Daoguang Tian,Bo Xiong,Xixian Xie
L-valine is an essential amino acid and an important amino acid in the food and feed industry. The relatively low titer and low fermentation yield currently limit the large-scale application of L-valine. Here, we constructed a chromosomally engineered Escherichia coli to efficiently produce L-valine. First, the synthetic pathway of L-valine was enhanced by heterologous introduction of a feedback-resistant
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Novel two-stage processes for optimal chemical production in microbes. Metab. Eng. (IF 7.263) Pub Date : 2020-08-19 Kaushik Raj,Naveen Venayak,Radhakrishnan Mahadevan
Microbial metabolism can be harnessed to produce a broad range of industrially important chemicals. Often, three key process variables: Titer, Rate and Yield (TRY) are the target of metabolic engineering efforts to improve microbial hosts toward industrial production. Previous research into improving the TRY metrics have examined the efficacy of having distinct growth and production stages to achieve
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Dynamic control in metabolic engineering: Theories, tools, and applications. Metab. Eng. (IF 7.263) Pub Date : 2020-09-11 Christopher J Hartline,Alexander C Schmitz,Yichao Han,Fuzhong Zhang
Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically
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High-yield whole cell biosynthesis of Nylon 12 monomer with self-sufficient supply of multiple cofactors. Metab. Eng. (IF 7.263) Pub Date : 2020-09-11 Jiawei Ge,Xiaohong Yang,Hongwei Yu,Lidan Ye
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Promiscuous phosphoketolase and metabolic rewiring enables novel non-oxidative glycolysis in yeast for high-yield production of acetyl-CoA derived products. Metab. Eng. (IF 7.263) Pub Date : 2020-09-08 John Hellgren,Alexei Godina,Jens Nielsen,Verena Siewers
Carbon-conserving pathways have the potential of increasing product yields in biotechnological processes. The aim of this project was to investigate the functionality of a novel carbon-conserving pathway that produces 3 mol of acetyl-CoA from fructose-6-phosphate without carbon loss in the yeast Saccharomyces cerevisiae. This cyclic pathway relies on a generalist phosphoketolase (Xfspk), which can
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Development of Klebsiella pneumoniae J2B as microbial cell factory for the production of 1,3-propanediol from glucose. Metab. Eng. (IF 7.263) Pub Date : 2020-09-06 Suman Lama,Eunhee Seol,Sunghoon Park
1,3-Propanediol (1,3-PDO) is an important platform chemical which has a wide application in food, cosmetics, pharmaceutical and textile industries. Its biological production using recombinant Escherichia coli with glucose as carbon source has been commercialized by DuPont, but E. coli cannot synthesize coenzyme B12 which is an essential and expensive cofactor of glycerol dehydratase, a core enzyme
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Engineering cyanobacteria as cell factories for direct trehalose production from CO2. Metab. Eng. (IF 7.263) Pub Date : 2020-09-06 Yue Qiao,Weihua Wang,Xuefeng Lu
Trehalose is a non-reducing disaccharide with a wide range of applications in food, cosmetic, and pharmaceutical industries. Cyanobacteria are promising cell factories to produce biochemicals by using solar energy and CO2. Trehalose is biosynthesized at low intracellular concentrations as a salt-inducible compatible solute in some cyanobacteria. In the current study, we demonstrated the efficient trehalose
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Revealing metabolic mechanisms of interaction in the anaerobic digestion microbiome by flux balance analysis. Metab. Eng. (IF 7.263) Pub Date : 2020-09-06 Arianna Basile,Stefano Campanaro,Adam Kovalovszki,Guido Zampieri,Alessandro Rossi,Irini Angelidaki,Giorgio Valle,Laura Treu
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Engineering carotenoid production in mammalian cells for nutritionally enhanced cell-cultured foods. Metab. Eng. (IF 7.263) Pub Date : 2020-09-02 Andrew J Stout,Addison B Mirliani,Erin L Soule-Albridge,Julian M Cohen,David L Kaplan
Metabolic engineering of mammalian cells has to-date focused primarily on biopharmaceutical protein production or the manipulation of native metabolic processes towards therapeutic aims. However, significant potential exists for expanding these techniques to diverse applications by looking across the taxonomic tree to bioactive metabolites not synthesized in animals. Namely, cross-taxa metabolic engineering
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Characterization and directed evolution of propionyl-CoA carboxylase and its application in succinate biosynthetic pathway with two CO2 fixation reactions. Metab. Eng. (IF 7.263) Pub Date : 2020-08-26 Xiutao Liu,Xinjun Feng,Yamei Ding,Wenjie Gao,Mo Xian,Jichao Wang,Guang Zhao
Propionyl-CoA carboxylase (PCC) is a promising enzyme in the fields of biological CO2 utilization, synthesis of natrual products, and so on. The activity and substrate specificity of PCC are dependent on its key subunit carboxyltransferase (CT). To obtain PCC with high enzyme activity, seven pccB genes encoding CT subunit from diverse microorganisms were expressed in recombinant E. coli, and PccB from
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Punicic acid production in Brassica napus. Metab. Eng. (IF 7.263) Pub Date : 2020-08-22 Yang Xu,Elzbieta Mietkiewska,Saleh Shah,Randall J Weselake,Guanqun Chen
Punicic acid (PuA; 18:3Δ9cis,11trans,13cis), a conjugated linolenic acid isomer bearing three conjugated double bonds, is associated with various health benefits and has potential for industrial use. The major nature source of this unusual fatty acid is pomegranate (Punica granatum) seed oil, which contains up to 80% (w/w) of its fatty acids as PuA. Pomegranate seed oil, however, is low yielding with
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Engineering Saccharomyces cerevisiae for high yield production of α-amyrin via synergistic remodeling of α-amyrin synthase and expanding the storage pool. Metab. Eng. (IF 7.263) Pub Date : 2020-08-22 Yuan Yu,Aamir Rasool,Haoran Liu,Bo Lv,Pengcheng Chang,Hao Song,Ying Wang,Chun Li
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Engineered Pseudomonas putida simultaneously catabolizes five major components of corn stover lignocellulose: Glucose, xylose, arabinose, p-coumaric acid, and acetic acid. Metab. Eng. (IF 7.263) Pub Date : 2020-08-20 Joshua R Elmore,Gara N Dexter,Davinia Salvachúa,Marykate O'Brien,Dawn M Klingeman,Kent Gorday,Joshua K Michener,Darren J Peterson,Gregg T Beckham,Adam M Guss
Valorization of all major lignocellulose components, including lignin, cellulose, and hemicellulose is critical for an economically viable bioeconomy. In most biochemical conversion approaches, the standard process separately upgrades sugar hydrolysates and lignin. Here, we present a new process concept based on an engineered microbe that could enable simultaneous upgrading of all lignocellulose streams
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Engineering the oleaginous yeast Yarrowia lipolytica for high-level resveratrol production. Metab. Eng. (IF 7.263) Pub Date : 2020-08-18 Javier Sáez-Sáez,Guokun Wang,Eko Roy Marella,Suresh Sudarsan,Marc Cernuda Pastor,Irina Borodina
Resveratrol is a plant secondary metabolite with multiple health-beneficial properties. Microbial production of resveratrol in model microorganisms requires extensive engineering to reach commercially viable levels. Here, we explored the potential of the non-conventional yeast Yarrowia lipolytica to produce resveratrol and several other shikimate pathway-derived metabolites (p-coumaric acid, cis,cis-muconic
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High titer methyl ketone production with tailored Pseudomonas taiwanensis VLB120. Metab. Eng. (IF 7.263) Pub Date : 2020-08-15 Salome C Nies,Tobias B Alter,Sophia Nölting,Susanne Thiery,An N T Phan,Noud Drummen,Jay D Keasling,Lars M Blank,Birgitta E Ebert
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Replacing the Calvin cycle with the reductive glycine pathway in Cupriavidus necator. Metab. Eng. (IF 7.263) Pub Date : 2020-08-15 Nico J Claassens,Guillermo Bordanaba-Florit,Charles A R Cotton,Alberto De Maria,Max Finger-Bou,Lukas Friedeheim,Natalia Giner-Laguarda,Martí Munar-Palmer,William Newell,Giovanni Scarinci,Jari Verbunt,Stijn T de Vries,Suzan Yilmaz,Arren Bar-Even
Formate can be directly produced from CO2 and renewable electricity, making it a promising microbial feedstock for sustainable bioproduction. Cupriavidus necator is one of the few biotechnologically-relevant hosts that can grow on formate, but it uses the Calvin cycle, the high ATP cost of which limits biomass and product yields. Here, we redesign C. necator metabolism for formate assimilation via
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High-level production of ornithine by expression of the feedback inhibition-insensitive N-acetyl glutamate kinase in the sake yeast Saccharomyces cerevisiae. Metab. Eng. (IF 7.263) Pub Date : 2020-08-14 Masataka Ohashi,Ryo Nasuno,Shota Isogai,Hiroshi Takagi
We previously reported that intracellular proline (Pro) confers tolerance to ethanol on the yeast Saccharomyces cerevisiae. In this study, to improve the ethanol productivity of sake, a traditional Japanese alcoholic beverage, we successfully isolated several Pro-accumulating mutants derived from diploid sake yeast of S. cerevisiae by a conventional mutagenesis. Interestingly, one of them (strain A902-4)
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Production of multiple terpenes of different chain lengths by subcellular targeting of multi-substrate terpene synthase in plants. Metab. Eng. (IF 7.263) Pub Date : 2020-08-11 Savitha Dhandapani,Jessica Gambino Tjhang,In-Cheol Jang
Multi-substrate terpene synthases (TPSs) are distinct from typical TPSs that react with a single substrate. Although in vitro activity of few multi-substrate TPSs have been reported, in vivo characterization has not been well investigated for most of them. Here, a new TPS from Cananga odorata, CoTPS5, belonging to TPS-f subfamily was functionally characterized in vitro as well as in vivo. CoTPS5 reacted
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Comprehensive study on Escherichia coli genomic expression: Does position really matter? Metab. Eng. (IF 7.263) Pub Date : 2020-08-11 Anke R Goormans,Nico Snoeck,Hannes Decadt,Karel Vermeulen,Gert Peters,Pieter Coussement,Dries Van Herpe,Joeri J Beauprez,Sofie L De Maeseneire,Wim K Soetaert
As a biorefinery platform host, Escherichia coli has been used extensively to produce metabolites of commercial interest. Integration of foreign DNA onto the bacterial genome allows for stable expression overcoming the need for plasmid expression and its associated instability. Despite the development of numerous tools and genome editing technologies, the question of where to incorporate a synthetic
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Engineering of the 2,3-butanediol pathway of Paenibacillus polymyxa DSM 365. Metab. Eng. (IF 7.263) Pub Date : 2020-08-07 Christoph Schilling,Rosario Ciccone,Volker Sieber,Jochen Schmid
Paenibacillus polymyxa is a Gram-positive, non-pathogenic soil bacterium that has been extensively investigated for the production of R-,R-2,3-butanediol in exceptionally high enantiomeric purity. Rational metabolic engineering efforts to increase productivity and product titers were restricted due to limited genetic accessibility of the organism up to now. By use of CRISPR-Cas9 mediated genome editing
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A bimodular PKS platform that expands the biological design space. Metab. Eng. (IF 7.263) Pub Date : 2020-08-06 Amin Zargar,Luis Valencia,Jessica Wang,Ravi Lal,Samantha Chang,Miranda Werts,Andrew R Wong,Amanda C Hernández,Veronica Benites,Edward E K Baidoo,Leonard Katz,Jay D Keasling
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