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Co-cultivation of Saccharomyces cerevisiae strains combines advantages of different metabolic engineering strategies for improved ethanol yield Metab. Eng. (IF 8.4) Pub Date : 2023-09-24 Aafke C.A. van Aalst, Igor S. van der Meulen, Mickel L.A. Jansen, Robert Mans, Jack T. Pronk
Glycerol is the major organic byproduct of industrial ethanol production with the yeast Saccharomyces cerevisiae. Improved ethanol yields have been achieved with engineered S. cerevisiae strains in which heterologous pathways replace glycerol formation as the predominant mechanism for anaerobic re-oxidation of surplus NADH generated in biosynthetic reactions. Functional expression of heterologous phosphoribulokinase
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Electrical-biological hybrid system for carbon efficient isobutanol production Metab. Eng. (IF 8.4) Pub Date : 2023-09-20 Tanner R. Treece, Santanu Pattanayak, Morgan M. Matson, Mateo M. Cepeda, Louise A. Berben, Shota Atsumi
We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO2 to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO2 sequestration is notoriously slow compared to electrochemical CO2 reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form
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Controlling circuitry dictates the growth optimization of Saccharomyces cerevisiae Metab. Eng. (IF 8.4) Pub Date : 2023-09-21 Viviana Nguyen, Pu Xue, Yifei Li, Huimin Zhao, Ting Lu
Microbial growth emerges from coordinated synthesis of various cellular components from limited resources. In Saccharomyces cerevisiae, cyclic AMP (cAMP)-mediated signaling is shown to orchestrate cellular metabolism; however, it remains unclear quantitatively how the controlling circuit drives resource partition and subsequently shapes biomass growth. Here we combined experiment with mathematical
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Deep learning for metabolic pathway design Metab. Eng. (IF 8.4) Pub Date : 2023-09-19 Gahyeon Ryu, Gi Bae Kim, Taeho Yu, Sang Yup Lee
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Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction Metab. Eng. (IF 8.4) Pub Date : 2023-09-17 Xu Gong, Hongwei Geng, Yun Yang, Shuyi Zhang, Zilong He, Yubo Fan, Fengyi Yin, Zhifa Zhang, Guo-Qiang Chen
An overwhelming number of studies have reported the correlation of decreased abundance of butyrate-producing commensals with a wide range of diseases. However, the molecular-level mechanisms whereby gut butyrate causally affects the host mucosal immunity and pathogenesis were poorly understood, hindered by the lack of efficient tools to control intestinal butyrate. Here we engineered a facultative
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Large-scale pathway reconstruction and colorimetric screening accelerate cellular metabolism engineering Metab. Eng. (IF 8.4) Pub Date : 2023-09-17 Xiangxiang Wang, Yuyu Zhao, Zhaohua Hou, Xiaoxu Chen, Shuangying Jiang, Wei Liu, Xin Hu, Junbiao Dai, Guanghou Zhao
The capability to manipulate and analyze hard-wired metabolic pathways sets the pace at which we can engineer cellular metabolism. Here, we present a framework to extensively rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and readily assess malonyl-CoA output based on pathway-scale DNA reconstruction in combination with colorimetric screening (Pracs). We applied Pracs to
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Mitigating transcriptional bottleneck using a constitutively active transcription factor, VP16-CREB, in mammalian cells Metab. Eng. (IF 8.4) Pub Date : 2023-09-12 Chansik Yoon, Kyoung Eun Baek, Dongil Kim, Gyun Min Lee
High-level expression of recombinant proteins in mammalian cells has long been an area of interest. Inefficient transcription machinery is often an obstacle in achieving high-level expression of recombinant proteins in mammalian cells. Synthetic promoters have been developed to improve the transcription efficiency, but have achieved limited success due to the limited availability of transcription factors
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Metabolic engineering of Synechococcus elongatus 7942 for enhanced sucrose biosynthesis Metab. Eng. (IF 8.4) Pub Date : 2023-09-09 Bo Wang, Cristal Zuniga, Michael T. Guarnieri, Karsten Zengler, Michael Betenbaugh, Jamey D. Young
The capability of cyanobacteria to produce sucrose from CO2 and light has a remarkable societal and biotechnological impact since sucrose can serve as a carbon and energy source for a variety of heterotrophic organisms and can be converted into value-added products. However, most metabolic engineering efforts have focused on understanding local pathway alterations that drive sucrose biosynthesis and
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Engineering acetylation platform for the total biosynthesis of D-amino acids Metab. Eng. (IF 8.4) Pub Date : 2023-09-09 Yanqi Bi, Jingyu Wang, Jialong Li, Hsiang-Hui Chou, Tianhua Ren, Jinlin Li, Kechun Zhang
Optically pure D-amino acids are key chemicals with various applications. Although the production of specific D-amino acids has been achieved by chemical synthesis or with in vitro enzyme catalysts, it is challenging to convert a simple carbon source into D-amino acids with high efficiency. Here, we design an artificial metabolic pathway by engineering bacteria to heterologously express racemase and
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Identification of hyperosmotic stress-responsive genes in Chinese hamster ovary cells via genome-wide virus-free CRISPR/Cas9 screening Metab. Eng. (IF 8.4) Pub Date : 2023-09-12 Su Hyun Kim, Seunghyeon Shin, Minhye Baek, Kai Xiong, Karen Julie la Cour Karottki, Hooman Hefzi, Lise Marie Grav, Lasse Ebdrup Pedersen, Helene Faustrup Kildegaard, Nathan E. Lewis, Jae Seong Lee, Gyun Min Lee
Chinese hamster ovary (CHO) cells are the preferred mammalian host cells for therapeutic protein production that have been extensively engineered to possess the desired attributes for high-yield protein production. However, empirical approaches for identifying novel engineering targets are laborious and time-consuming. Here, we established a genome-wide CRISPR/Cas9 screening platform for CHO–K1 cells
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Combinatorial optimization and spatial remodeling of CYPs to control product profile Metab. Eng. (IF 8.4) Pub Date : 2023-09-12 Jiazeng Yang, Yuguang Liu, Dacai Zhong, Linlin Xu, Haixin Gao, Jay D. Keasling, Xiaozhou Luo, Howard H. Chou
Activating inert substrates is a challenge in nature and synthetic chemistry, but essential for creating functionally active molecules. In this work, we used a combinatorial optimization approach to assemble cytochrome P450 monooxygenases (CYPs) and reductases (CPRs) to achieve a target product profile. By creating 110 CYP-CPR pairs and iteratively screening different pairing libraries, we demonstrated
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Multi-omics view of recombinant Yarrowia lipolytica: Enhanced ketogenic amino acid catabolism increases polyketide-synthase-driven docosahexaenoic production to high selectivity at the gram scale Metab. Eng. (IF 8.4) Pub Date : 2023-09-07 Sofija Jovanovic Gasovic, Demian Dietrich, Lars Gläser, Peng Cao, Michael Kohlstedt, Christoph Wittmann
DHA is a marine PUFA of commercial value, given its multiple health benefits. The worldwide emerging shortage in DHA supply has increased interest in microbial cell factories that can provide the compound de novo. In this regard, the present work aimed to improve DHA production in the oleaginous yeast strain Y. lipolytica Af4, which synthetized the PUFA via a heterologous myxobacterial polyketide synthase
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A reactive species reactions module for integration into genome-scale metabolic models for improved insights: Application to cancer Metab. Eng. (IF 8.4) Pub Date : 2023-09-07 Subasree Sridhar, Prerna Bhalla, Justin Kullu, Sriya Veerapaneni, Swagatika Sahoo, Nirav Bhatt, G.K. Suraishkumar
Reactive species (RS) play significant roles in many disease contexts. Despite their crucial roles in diseases including cancer, the RS are not adequately modeled in the genome-scale metabolic (GSM) models, which are used to understand cell metabolism in disease contexts. We have developed a scalable RS reactions module that can be integrated with any Recon 3D-derived human metabolic model, or after
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Metabolic regulation of Shewanella oneidensis for microbial electrosynthesis: From extracellular to intracellular Metab. Eng. (IF 8.4) Pub Date : 2023-09-04 Yixin Li, Qingliu Luo, Jiaying Su, Guowen Dong, Mingfeng Cao, Yuanpeng Wang
Shewanella oneidensis MR-1 (S. oneidensis MR-1) has been shown to benefit from microbial electrosynthesis (MES) due to its exceptional electron transfer efficiency. In this study, genes involved in both extracellular electron uptake (EEU) and intracellular CO2 conversion processes were examined and regulated to enhance MES performance. The key genes identified for MES in the EEU process were mtrB,
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Metabolic engineering of Halomonas bluephagenesis for high-level mevalonate production from glucose and acetate mixture Metab. Eng. (IF 8.4) Pub Date : 2023-08-30 Jing Zhang, Yue Yuan, Zhiwen Wang, Tao Chen
Mevalonate (MVA) plays a crucial role as a building block for the biosynthesis of isoprenoids. In this study, we engineered Halomonas bluephagenesis to efficiently produce MVA. Firstly, by screening MVA synthetases from eight different species, the two efficient candidate modules, specifically NADPH-dependent mvaESEfa from Enterococcus faecalis and NADH-dependent mvaESLca from Lactobacillus casei,
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Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast Metab. Eng. (IF 8.4) Pub Date : 2023-08-22 Jiwei Mao, Marta Tous Mohedano, Jing Fu, Xiaowei Li, Quanli Liu, Jens Nielsen, Verena Siewers, Yun Chen
(2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related
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DRAGON: Harnessing the power of DNA repair for accelerating genome evolution in Corynebacterium glutamicum Metab. Eng. (IF 8.4) Pub Date : 2023-08-12 Yun Ju, Hongyu Zhang, Xiaocong Du, Jingxuan Wei, Jun Liu, Liang Wei, Qingdai Liu, Ning Xu
Hypermutation is a robust phenotype characterized by high elevation of spontaneous mutation rates, which has been shown to facilitate rapid adaptation to the stressful environments by hitchhiking with favorable mutations. Accumulating evidence argues that deficient DNA repair can give rise to hypermutation events in bacteria. Here, we provided a comprehensive survey of DNA repair systems to identify
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Engineering low-salt growth Halomonas Bluephagenesis for cost-effective bioproduction combined with adaptive evolution Metab. Eng. (IF 8.4) Pub Date : 2023-08-04 Lizhan Zhang, Yina Lin, Xueqing Yi, Wuzhe Huang, Qitiao Hu, Zhongnan Zhang, Fuqing Wu, Jian-wen Ye, Guo-Qiang Chen
Halophilic Halomonas bluephagenesis has been engineered to produce various added-value bio-compounds with reduced costs. However, the salt-stress regulatory mechanism remained unclear. H. bluephagenesis was randomly mutated to obtain low-salt growing mutants via atmospheric and room temperature plasma (ARTP). The resulted H. bluephagenesis TDH4A1B5 was constructed with the chromosomal integration of
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Fluctuating pH for efficient photomixotrophic succinate production Metab. Eng. (IF 8.4) Pub Date : 2023-07-26 Tanner R. Treece, Marissa Tessman, Robert S. Pomeroy, Stephen P. Mayfield, Ryan Simkovsky, Shota Atsumi
Cyanobacteria are attracting increasing attention as a photosynthetic chassis organism for diverse biochemical production, however, photoautotrophic production remains inefficient. Photomixotrophy, a method where sugar is used to supplement baseline autotrophic metabolism in photosynthetic hosts, is becoming increasingly popular for enhancing sustainable bioproduction with multiple input energy streams
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A robust genetic toolbox for fine-tuning gene expression in the CO2-Fixing methanogenic archaeon Methanococcus maripaludis Metab. Eng. (IF 8.4) Pub Date : 2023-07-24 Qing Xu, Qing Du, Jian Gao, Lei Chen, Xiuzhu Dong, Jie Li
Libraries of well-characterized genetic elements for fine-tuning gene expression are essential for biological and biotechnological research and applications. The fast-growing and genetically tractable methanogen, Methanococcus maripaludis, is a promising host organism for biotechnological conversion of carbon dioxide and renewable hydrogen into fuels and value-added products, as well as fundamental
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Engineering Escherichia coli for selective 1-decanol production using the reverse β-oxidation (rBOX) pathway Metab. Eng. (IF 8.4) Pub Date : 2023-07-21 Jing Chen, Ramon Gonzalez
1-Decanol has great value in the pharmaceutical and fragrance industries and plays an important role in the chemical industry. In this study, we engineered Escherichia coli to selectively synthesize 1-decanol by using enzymes of the core reverse β-oxidation (rBOX) pathway and termination module with overlapping chain-length specificity. Through screening for acyl-CoA reductase termination enzymes and
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Overexpression of peroxisome proliferator-activated receptor γ co-activator-1⍺ (PGC-1⍺) in Chinese hamster ovary cells increases oxidative metabolism and IgG productivity Metab. Eng. (IF 8.4) Pub Date : 2023-07-18 Sarah A. Sacco, Allison G. McAtee Pereira, Irina Trenary, Kevin D. Smith, Michael J. Betenbaugh, Jamey D. Young
Chinese hamster ovary (CHO) cells are used extensively to produce protein therapeutics, such as monoclonal antibodies (mAbs), in the biopharmaceutical industry. MAbs are large proteins that are energetically demanding to synthesize and secrete; therefore, high-producing CHO cell lines that are engineered for maximum metabolic efficiency are needed to meet increasing demands for mAb production. Previous
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Time-resolved, deuterium-based fluxomics uncovers the hierarchy and dynamics of sugar processing by Pseudomonas putida Metab. Eng. (IF 8.4) Pub Date : 2023-07-16 Daniel C. Volke, Nicolas Gurdo, Riccardo Milanesi, Pablo I. Nikel
Pseudomonas putida, a microbial host widely adopted for metabolic engineering, processes glucose through convergent peripheral pathways that ultimately yield 6-phosphogluconate. The periplasmic gluconate shunt (PGS), composed by glucose and gluconate dehydrogenases, sequentially transforms glucose into gluconate and 2-ketogluconate. Although the secretion of these organic acids by P. putida has been
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Metabolic engineering of Corynebacterium glutamicum for the high-level production of valerolactam, a nylon-5 monomer Metab. Eng. (IF 8.4) Pub Date : 2023-07-12
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Minimized antibiotic-free plasmid vector for gene therapy utilizing a new toxin-antitoxin system Metab. Eng. (IF 8.4) Pub Date : 2023-07-13 Zhe Chen, Jianyun Yao, Pingjing Zhang, Pengxia Wang, Songwei Ni, Tao Liu, Yi Zhao, Kaihao Tang, Yan Sun, Qijun Qian, Xiaoxue Wang
Approaches to improve plasmid-mediated transgene expression are needed for gene therapy and genetic immunization applications. The backbone sequences needed for the production of plasmids in bacterial hosts and the use of antibiotic resistance genes as selection markers represent biological safety risks. Here, we report the development of an antibiotic-free expression plasmid vector with a minimized
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Towards universal synthetic heterotrophy using a metabolic coordinator Metab. Eng. (IF 8.4) Pub Date : 2023-07-04 Sean F. Sullivan, Anuj Shetty, Tharun Bharadwaj, Naveen Krishna, Vikas D. Trivedi, Venkatesh Endalur Gopinarayanan, Todd C. Chappell, Daniel M. Sellers, R. Pravin Kumar, Nikhil U. Nair
Engineering the utilization of non-native substrates, or synthetic heterotrophy, in proven industrial microbes such as Saccharomyces cerevisiae represents an opportunity to valorize plentiful and renewable sources of carbon and energy as inputs to bioprocesses. We previously demonstrated that activation of the galactose (GAL) regulon, a regulatory structure used by this yeast to coordinate substrate
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Vitamin E biofortification: Maximizing oilseed tocotrienol and total vitamin E tocochromanol production by use of metabolic bypass combinations Metab. Eng. (IF 8.4) Pub Date : 2023-07-08 Anji Reddy Konda, Malleswari Gelli, Connor Pedersen, Rebecca E. Cahoon, Chunyu Zhang, Toshihiro Obata, Edgar B. Cahoon
Vitamin E tocochromanols are generated in plants by prenylation of homogentisate using geranylgeranyl diphosphate (GGDP) for tocotrienol biosynthesis and phytyl diphosphate (PDP) for tocopherol biosynthesis. Homogentisate geranylgeranyl transferase (HGGT), which uses GGDP for prenylation, is a proven target for oilseed tocochromanol biofortification that effectively bypasses the chlorophyll-linked
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Optogenetic control of Cdc48 for dynamic metabolic engineering in yeast Metab. Eng. (IF 8.4) Pub Date : 2023-07-07 Filipp Bezold, Johannes Scheffer, Philipp Wendering, Zahra Razaghi-Moghadam, Jonathan Trauth, Bastian Pook, Hagen Nußhär, Sophia Hasenjäger, Zoran Nikoloski, Lars-Oliver Essen, Christof Taxis
Dynamic metabolic engineering is a strategy to switch key metabolic pathways in microbial cell factories from biomass generation to accumulation of target products. Here, we demonstrate that optogenetic intervention in the cell cycle of budding yeast can be used to increase production of valuable chemicals, such as the terpenoid β-carotene or the nucleoside analog cordycepin. We achieved optogenetic
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Designing glucose utilization "highway" for recombinant biosynthesis Metab. Eng. (IF 8.4) Pub Date : 2023-06-30 Xuanxuan Zhang, Yufeng Cao, Ying Liu, Yanyan Lei, Ruixue Zhai, Wei Chen, Guizhi Shi, Jian-Ming Jin, Chaoning Liang, Shuang-Yan Tang
cAMP receptor protein (CRP) is known as a global regulatory factor mainly mediating carbon source catabolism. Herein, we successfully engineered CRP to develop microbial chassis cells with improved recombinant biosynthetic capability in minimal medium with glucose as single carbon source. The obtained best-performing cAMP-independent CRPmu9 mutant conferred both faster cell growth and a 133-fold improvement
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Engineering the biological conversion of formate into crotonate in Cupriavidus necator Metab. Eng. (IF 8.4) Pub Date : 2023-07-04 Florent Collas, Beau B. Dronsella, Armin Kubis, Karin Schann, Sebastian Binder, Nils Arto, Nico J. Claassens, Frank Kensy, Enrico Orsi
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Laboratory evolution of Synechocystis sp. PCC 6803 for phenylpropanoid production Metab. Eng. (IF 8.4) Pub Date : 2023-06-29 Kateryna Kukil, Elias Englund, Nick Crang, Elton P. Hudson, Pia Lindberg
Cyanobacteria are promising as a biotechnological platform for production of various industrially relevant compounds, including aromatic amino acids and their derivatives, phenylpropanoids. In this study, we have generated phenylalanine resistant mutant strains (PRMs) of the unicellular cyanobacterium Synechocystis sp. PCC 6803, by laboratory evolution under the selective pressure of phenylalanine
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Engineering Escherichia coli to produce aromatic chemicals from ethylene glycol Metab. Eng. (IF 8.4) Pub Date : 2023-06-29 Smaranika Panda, Jie Fu J. Zhou, Michelle Feigis, Emma Harrison, Xiaoqiang Ma, Vincent Fung Kin Yuen, Radhakrishnan Mahadevan, Kang Zhou
Microbial overproduction of aromatic chemicals has gained considerable industrial interest and various metabolic engineering approaches have been employed in recent years to address the associated challenges. So far, most studies have used sugars (mostly glucose) or glycerol as the primary carbon source. In this study, we used ethylene glycol (EG) as the main carbon substrate. EG could be obtained
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Population genomics-guided engineering of phenazine biosynthesis in Pseudomonas chlororaphis Metab. Eng. (IF 8.4) Pub Date : 2023-06-25 Sarah Thorwall, Varun Trivedi, Eva Ottum, Ian Wheeldon
The emergence of next-generation sequencing (NGS) technologies has made it possible to not only sequence entire genomes, but also identify metabolic engineering targets across the pangenome of a microbial population. This study leverages NGS data as well as existing molecular biology and bioinformatics tools to identify and validate genomic signatures for improving phenazine biosynthesis in Pseudomonas
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Metabolic engineering of human gut microbiome: Recent developments and future perspectives Metab. Eng. (IF 8.4) Pub Date : 2023-06-24 Peishun Li, Stefan Roos, Hao Luo, Boyang Ji, Jens Nielsen
Many studies have demonstrated that the gut microbiota is associated with human health and disease. Manipulation of the gut microbiota, e.g. supplementation of probiotics, has been suggested to be feasible, but subject to limited therapeutic efficacy. To develop efficient microbiota-targeted diagnostic and therapeutic strategies, metabolic engineering has been applied to construct genetically modified
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A genome-scale dynamic constraint-based modelling (gDCBM) framework predicts growth dynamics, medium composition and intracellular flux distributions in CHO clonal variations Metab. Eng. (IF 8.4) Pub Date : 2023-06-20 Mohammadreza Yasemi, Mario Jolicoeur
Optimizing mammalian cell growth and bioproduction is a tedious task. However, due to the inherent complexity of eukaryotic cells, heuristic experimental approaches such as, metabolic engineering and bioprocess design, are frequently integrated with mathematical models of cell culture to improve biological process efficiency and find paths for improvement. Constraint-based metabolic models have evolved
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Consolidated bioprocessing for bioethanol production by metabolically engineered cellulolytic fungus Myceliophthora thermophila Metab. Eng. (IF 8.4) Pub Date : 2023-06-20 Yongli Zhang, Tao Sun, Taju Wu, Jinyang Li, Die Hu, Defei Liu, Jingen Li, Chaoguang Tian
Using cellulosic ethanol as fuel is one way to help achieve the world's decarbonization goals. However, the economics of the present technology are unfavorable, especially the cost of cellulose degradation. Here, we reprogram the thermophilic cellulosic fungus Myceliophthora thermophila to directly ferment cellulose into ethanol by mimicking the aerobic ethanol fermentation of yeast (the Crabtree effect)
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A landing pad system for multicopy gene integration in Issatchenkia orientalis Metab. Eng. (IF 8.4) Pub Date : 2023-06-19 Zia Fatma, Shih-I Tan, Aashutosh Girish Boob, Huimin Zhao
The robust nature of the non-conventional yeast Issatchenkia orientalis allows it to grow under highly acidic conditions and therefore, has gained increasing interest in producing organic acids using a variety of carbon sources. Recently, the development of a genetic toolbox for I. orientalis, including an episomal plasmid, characterization of multiple promoters and terminators, and CRISPR-Cas9 tools
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A novel toolbox for precise regulation of gene expression and metabolic engineering in Bacillus licheniformis Metab. Eng. (IF 8.4) Pub Date : 2023-06-10 Yi Rao, Jiaqi Wang, Xinyuan Yang, Xinxin Xie, Yangyang Zhan, Xin Ma, Dongbo Cai, Shouwen Chen
Despite industrial bio-manufacturing progress using Bacillus licheniformis, the absence of a well-characterized toolbox allowing precise regulation of multiple genes limits its expansion for basic research and application. Here, a novel gene expression toolbox (GET) was developed for precise regulation of gene expression and high-level production of 2-phenylethanol. Firstly, we established a novel
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Microbial production of trans-aconitic acid Metab. Eng. (IF 8.4) Pub Date : 2023-06-12 Ce Geng, Zhigang Jin, Meng Gu, Jibin Li, Shen Tang, Qiang Guo, Yunpeng Zhang, Wei Zhang, Yuezhong Li, Xuenian Huang, Xuefeng Lu
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Metabolic engineering to produce palmitic acid or palmitoleic acid in an oleic acid-producing Corynebacterium glutamicum strain Metab. Eng. (IF 8.4) Pub Date : 2023-06-05 Seiki Takeno, Yosuke Hirata, Kako Kitamura, Tatsunori Ohtake, Kuniyoshi Aoki, Noriko Murata, Mikiro Hayashi, Masato Ikeda
Focusing on the differences in the catalytic properties of two type I fatty acid synthases FasA and FasB, the fasA gene was disrupted in an oleic acid-producing Corynebacterium glutamicum strain. The resulting oleic acid-requiring strain whose fatty acid synthesis depends only on FasB exhibited almost exclusive production (217 mg/L) of palmitic acid (C16:0) from 1% glucose under the conditions supplemented
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High-level and -yield production of L-leucine in engineered Escherichia coli by multistep metabolic engineering Metab. Eng. (IF 8.4) Pub Date : 2023-06-05 Xiaohu Ding, Wenjun Yang, Xiaobin Du, Ning Chen, Qingyang Xu, Minhua Wei, Chenglin Zhang
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Rank-ordering of known enzymes as starting points for re-engineering novel substrate activity using a convolutional neural network Metab. Eng. (IF 8.4) Pub Date : 2023-06-08 Vikas Upadhyay, Veda Sheersh Boorla, Costas D. Maranas
Retro-biosynthetic approaches have made significant advances in predicting synthesis routes of target biofuel, bio-renewable or bio-active molecules. The use of only cataloged enzymatic activities limits the discovery of new production routes. Recent retro-biosynthetic algorithms increasingly use novel conversions that require altering the substrate or cofactor specificities of existing enzymes while
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Boosting titers of engineered triketide and tetraketide synthases to record levels through T7 promoter tuning Metab. Eng. (IF 8.4) Pub Date : 2023-05-29 Jie Zhang, Ramesh Bista, Takeshi Miyazawa, Adrian T. Keatinge-Clay
Modular polyketide synthases (PKS's) are promising platforms for the rational engineering of designer polyketides and commodity chemicals, yet their low productivities are a barrier to the practical biosynthesis of these compounds. Previously, we engineered triketide lactone synthases such as Pik167 using the recently updated module definition and showed they generate hundreds of milligrams of product
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Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae Metab. Eng. (IF 8.4) Pub Date : 2023-05-29 Sojeong Kim, Beom Gi Park, Hyunbin Jin, Daeyeol Lee, Jie Ying Teoh, Yung Jae Kim, Sak Lee, Soo-Jung Kim, Sang Hyun Moh, Dongwon Yoo, Wonwoo Choi, Ji-Sook Hahn
Mycosporine-like amino acids (MAAs) are promising natural sunscreens mainly produced in marine organisms. Until now, metabolic engineering efforts to produce MAAs in heterologous hosts have mainly focused on shinorine production, and the low production levels are still not suitable for industrial applications. In this study, we successfully developed Saccharomyces cerevisiae strains that can efficiently
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“In vivo biosynthesis of N,N-dimethyltryptamine, 5-MeO-N,N-dimethyltryptamine, and bufotenine in E. coli” Metab. Eng. (IF 8.4) Pub Date : 2023-05-23 Lucas M. Friedberg, Abhishek K. Sen, Quynh Nguyen, Gabriel P. Tonucci, Elle B. Hellwarth, William J. Gibbons, J. Andrew Jones
N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell factories
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Metabolic engineering of the shikimate pathway in Amycolatopsis strains for optimized glycopeptide antibiotic production Metab. Eng. (IF 8.4) Pub Date : 2023-05-25 Valentina Goldfinger, Marius Spohn, Jens-Peter Rodler, Melanie Sigle, Andreas Kulik, Max J. Cryle, Johanna Rapp, Hannes Link, Wolfgang Wohlleben, Evi Stegmann
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Improving the soluble expression of difficult-to-express proteins in prokaryotic expression system via protein engineering and synthetic biology strategies Metab. Eng. (IF 8.4) Pub Date : 2023-05-25 Jin-Ping Chen, Jin-Song Gong, Chang Su, Heng Li, Zheng-Hong Xu, Jin-Song Shi
Solubility and folding stability are key concerns for difficult-to-express proteins (DEPs) restricted by amino acid sequences and superarchitecture, resolved by the precise distribution of amino acids and molecular interactions as well as the assistance of the expression system. Therefore, an increasing number of tools are available to achieve efficient expression of DEPs, including directed evolution
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Engineering a Pseudomonas taiwanensis 4-coumarate platform for production of para-hydroxy aromatics with high yield and specificity Metab. Eng. (IF 8.4) Pub Date : 2023-05-18 Benedikt Wynands, Franziska Kofler, Anka Sieberichs, Nadine da Silva, Nick Wierckx
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Omics data for sampling thermodynamically feasible kinetic models Metab. Eng. (IF 8.4) Pub Date : 2023-05-18 Marina de Leeuw, Marta R.A. Matos, Lars Keld Nielsen
Kinetic models are key to understanding and predicting the dynamic behaviour of metabolic systems. Traditional models require kinetic parameters which are not always available and are often estimated in vitro. Ensemble models overcome this challenge by sampling thermodynamically feasible models around a measured reference point. However, it is unclear if the convenient distributions used to generate
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Engineering Rhodosporidium toruloides for production of 3-hydroxypropionic acid from lignocellulosic hydrolysate Metab. Eng. (IF 8.4) Pub Date : 2023-05-16 Di Liu, Hee Jin Hwang, Peter B. Otoupal, Gina M. Geiselman, Joonhoon Kim, Kyle R. Pomraning, Young-Mo Kim, Nathalie Munoz, Carrie D. Nicora, Yuqian Gao, Kristin E. Burnum-Johnson, Oslo Jacobson, Samuel Coradetti, Jinho Kim, Shuang Deng, Ziyu Dai, Jan-Philip Prahl, Deepti Tanjore, Taek Soon Lee, Jon K. Magnuson, John M. Gladden
Microbial production of valuable bioproducts is a promising route towards green and sustainable manufacturing. The oleaginous yeast, Rhodosporidium toruloides, has emerged as an attractive host for the production of biofuels and bioproducts from lignocellulosic hydrolysates. 3-hydroxypropionic acid (3HP) is an attractive platform molecule that can be used to produce a wide range of commodity chemicals
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LncRNA analysis of mAb producing CHO clones reveals marker and engineering potential Metab. Eng. (IF 8.4) Pub Date : 2023-05-15 Neža Novak, Martina Baumann, Amy Friss, Victor Cairns, Christine DeMaria, Nicole Borth
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Alternative routes for production of the drug candidate d-chiro-inositol with Corynebacterium glutamicum using endogenous or promiscuous plant enzymes Metab. Eng. (IF 8.4) Pub Date : 2023-05-03 Paul Ramp, Christina Mack, Astrid Wirtz, Michael Bott
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A tRNA Modification-based strategy for Identifying amiNo acid Overproducers (AMINO) Metab. Eng. (IF 8.4) Pub Date : 2023-05-04 Hao Guo, Ning Wang, Tingting Ding, Bo Zheng, Liwei Guo, Chaoyong Huang, Wuyuan Zhang, Lichao Sun, Xiaoyan Ma, Yi-Xin Huo
Amino acids have a multi-billion-dollar market with rising demand, prompting the development of high-performance microbial factories. However, a general screening strategy applicable to all proteinogenic and non-proteinogenic amino acids is still lacking. Modification of the critical structure of tRNA could decrease the aminoacylation level of tRNA catalyzed by aminoacyl-tRNA synthetases. Involved
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Development of a Streptomyces-based system for facile thioholgamide library generation and analysis Metab. Eng. (IF 8.4) Pub Date : 2023-05-02 Maria Lopatniuk, Florian Riedel, Julia Wildfeuer, Marc Stierhof, Charlotte Dahlem, Alexandra K. Kiemer, Andriy Luzhetskyy
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Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice Metab. Eng. (IF 8.4) Pub Date : 2023-04-22 M Carmen Soler-Vázquez, María del Mar Romero, Marijana Todorcevic, Katia Delgado, Carles Calatayud, Aleyda Benitez -Amaro, Maria Teresa La Chica Lhoëst, Paula Mera, Sebastián Zagmutt, Marianela Bastías-Pérez, Kevin Ibeas, Núria Casals, Joan Carles Escolà-Gil, Vicenta Llorente-Cortés, Antonella Consiglio, Dolors Serra, Laura Herrero
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Systematic genetic modifications of cell wall biosynthesis enhanced the secretion and surface-display of polysaccharide degrading enzymes in Saccharomyces cerevisiae Metab. Eng. (IF 8.4) Pub Date : 2023-04-24 Nanzhu Chen, Shuo Yang, Dawei You, Junfeng Shen, Banlai Ruan, Mei Wu, Jianzhi Zhang, Xiaozhou Luo, Hongting Tang
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Combinatorial gene inactivation of aldehyde dehydrogenases mitigates aldehyde oxidation catalyzed by E. coli resting cells Metab. Eng. (IF 8.4) Pub Date : 2023-04-24 Neil D. Butler, Shelby R. Anderson, Roman M. Dickey, Priyanka Nain, Aditya M. Kunjapur
Aldehydes are attractive chemical targets both as end products in the flavors and fragrances industry and as synthetic intermediates due to their propensity for C–C bond formation. Here, we identify and address unexpected oxidation of a model collection of aromatic aldehydes, including many that originate from biomass degradation. When diverse aldehydes are supplemented to E. coli cells grown under
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Evaluating proteome allocation of Saccharomyces cerevisiae phenotypes with resource balance analysis Metab. Eng. (IF 8.4) Pub Date : 2023-04-18 Hoang V. Dinh, Costas D. Maranas
Saccharomyces cerevisiae is an important model organism and a workhorse in bioproduction. Here, we reconstructed a compact and tractable genome-scale resource balance analysis (RBA) model (i.e., named scRBA) to analyze metabolic fluxes and proteome allocation in a computationally efficient manner. Resource capacity models such as scRBA provide the quantitative means to identify bottlenecks in biosynthetic
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A detailed genome-scale metabolic model of Clostridium thermocellum investigates sources of pyrophosphate for driving glycolysis Metab. Eng. (IF 8.4) Pub Date : 2023-04-20 Wheaton L. Schroeder, Teun Kuil, Antonius J.A. van Maris, Daniel G. Olson, Lee R. Lynd, Costas D. Maranas
Lignocellulosic biomass is an abundant and renewable source of carbon for chemical manufacturing, yet it is cumbersome in conventional processes. A promising, and increasingly studied, candidate for lignocellulose bioprocessing is the thermophilic anaerobe Clostridium thermocellum given its potential to produce ethanol, organic acids, and hydrogen gas from lignocellulosic biomass under high substrate
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A contribution of metabolic engineering to addressing medical problems: Metabolic flux analysis Metab. Eng. (IF 8.4) Pub Date : 2023-04-17 GaRyoung Lee, Sang Mi Lee, Hyun Uk Kim
Metabolic engineering has served as a systematic discipline for industrial biotechnology as it has offered systematic tools and methods for strain development and bioprocess optimization. Because these metabolic engineering tools and methods are concerned with the biological network of a cell with emphasis on metabolic network, they have also been applied to a range of medical problems where better