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Engineering carbon source division of labor for efficient α-carotene production in Corynebacterium glutamicum Metab. Eng. (IF 6.8) Pub Date : 2024-06-18 Kai Li, Cheng Li, Chen-Guang Liu, Xin-Qing Zhao, Ruiwen Ou, Charles A. Swofford, Feng-Wu Bai, Gregory Stephanopoulos, Anthony J. Sinskey
Effective utilization of glucose, xylose, and acetate, common carbon sources in lignocellulose hydrolysate, can boost biomanufacturing economics. However, carbon leaks into biomass biosynthesis pathways instead of the intended target product remain to be optimized. This study aimed to enhance α-carotene production by optimizing glucose, xylose, and acetate utilization in a high-efficiency cell factory
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A long-term growth stable Halomonas sp. deleted with multiple transposases guided by its metabolic network model Halo-ecGEM Metab. Eng. (IF 6.8) Pub Date : 2024-06-18 Lizhan Zhang, Jian-Wen Ye, Gang Li, Helen Park, Hao Luo, Yina Lin, Shaowei Li, Weinan Yang, Yuying Guan, Fuqing Wu, Wuzhe Huang, Qiong Wu, Nigel S. Scrutton, Jens Nielsen, Guo-Qiang Chen
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Metabolic engineering of Pichia pastoris for overproduction of cis-trans nepetalactol Metab. Eng. (IF 6.8) Pub Date : 2024-06-17 Cuifang Ye, Mengxin Li, Jucan Gao, Yimeng Zuo, Feng Xiao, Xiaojing Jiang, Jintao Cheng, Lei Huang, Zhinan Xu, Jiazhang Lian
Monoterpene indole alkaloids (MIAs) are a group of plant-derived natural products with high-value medicinal properties. However, their availability for clinical application is limited due to challenges in plant extraction. Microbial production has emerged as a promising strategy to meet the clinical demands for MIAs. The biosynthetic pathway of nepetalactol, which serves as the universal iridoid scaffold
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Genome-scale models of metabolism and expression predict the metabolic burden of recombinant protein expression Metab. Eng. (IF 6.8) Pub Date : 2024-06-15 Omid Oftadeh, Vassily Hatzimanikatis
The production of recombinant proteins in a host using synthetic constructs such as plasmids comes at the cost of detrimental effects such as reduced growth, energetic inefficiencies, and other stress responses, collectively known as metabolic burden. Increasing the number of copies of the foreign gene increases the metabolic load but increases the expression of the foreign protein. Thus, there is
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Developing a novel heme biosensor to produce high-active hemoproteins in Pichia pastoris through comparative transcriptomics Metab. Eng. (IF 6.8) Pub Date : 2024-06-04 Fei Yu, Chenyang Li, Tao Zhang, Jingwen Zhou, Jianghua Li, Jian Chen, Guocheng Du, Xinrui Zhao
The development of a heme-responsive biosensor for dynamic pathway regulation in eukaryotes has never been reported, posing a challenge for achieving the efficient synthesis of multifunctional hemoproteins and maintaining intracellular heme homeostasis. Herein, a biosensor containing a newly identified heme-responsive promoter, CRISPR/dCas9, and a degradation tag N-degron was designed and optimized
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Systematic engineering for production of anti-aging sunscreen compound in Pseudomonas putida Metab. Eng. (IF 6.8) Pub Date : 2024-06-03 Ian S. Yunus, Graham A. Hudson, Yan Chen, Jennifer W. Gin, Joonhoon Kim, Edward E.K. Baidoo, Christopher J. Petzold, Paul D. Adams, Blake A. Simmons, Aindrila Mukhopadhyay, Jay D. Keasling, Taek Soon Lee
Sunscreen has been used for thousands of years to protect skin from ultraviolet radiation. However, the use of modern commercial sunscreen containing oxybenzone, ZnO, and TiO has raised concerns due to their negative effects on human health and the environment. In this study, we aim to establish an efficient microbial platform for production of shinorine, a UV light absorbing compound with anti-aging
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Deciphering nutritional stress responses via knowledge-enriched transcriptomics for microbial engineering Metab. Eng. (IF 6.8) Pub Date : 2024-05-31 Jongoh Shin, Daniel C. Zielinski, Bernhard O. Palsson
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De novo biosynthesis of 3-hydroxy-3-methylbutyrate as anti-catabolic supplement by metabolically engineered Escherichia coli Metab. Eng. (IF 6.8) Pub Date : 2024-05-28 Sally J. Huang, Martin J. Lai, Arvin Y. Chen, Ethan I. Lan
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Use of acetate as substrate for sustainable production of homoserine and threonine by Escherichia coli W3110: A modular metabolic engineering approach Metab. Eng. (IF 6.8) Pub Date : 2024-05-23 Toan Minh Vo, Joon Young Park, Donghyuk Kim, Sunghoon Park
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Engineering of Saccharomyces cerevisiae for enhanced metabolic robustness and L-lactic acid production from lignocellulosic biomass Metab. Eng. (IF 6.8) Pub Date : 2024-05-23 Bohyun Choi, Albert Tafur Rangel, Eduard J. Kerkhoven, Yvonne Nygård
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Engineering yeasts to Co-utilize methanol or formate coupled with CO2 fixation Metab. Eng. (IF 6.8) Pub Date : 2024-05-15 Yuanke Guo, Rui Zhang, Jing Wang, Ruirui Qin, Jiao Feng, Kequan Chen, Xin Wang
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Corrigendum to “Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae” [Metab. Eng. 83 (2024) 172–182] Metab. Eng. (IF 6.8) Pub Date : 2024-05-10 Na Zhang, Xiaohan Li, Qiang Zhou, Ying Zhang, Bo Lv, Bing Hu, Chun Li
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Modularized Engineering of Shewanella oneidensis MR-1 for Efficient and Directional Synthesis of 5-Aminolevulinic Acid Metab. Eng. (IF 6.8) Pub Date : 2024-05-06 Jie Wu, Jing Wu, Ru-Li He, Lan Hu, Dong-Feng Liu, Wen-Wei Li
MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in
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Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae Metab. Eng. (IF 6.8) Pub Date : 2024-04-20 Na Zhang, Xiaohan Li, Qiang Zhou, Ying Zhang, Bo Lv, Bing Hu, Chun Li
Microbial bioengineering is a growing field for producing plant natural products (PNPs) in recent decades, using heterologous metabolic pathways in host cells. Once heterologous metabolic pathways have been introduced into host cells, traditional metabolic engineering techniques are employed to enhance the productivity and yield of PNP biosynthetic routes, as well as to manage competing pathways. The
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Serial adaptive laboratory evolution enhances mixed carbon metabolic capacity of Escherichia coli Metab. Eng. (IF 6.8) Pub Date : 2024-04-16 Kangsan Kim, Donghui Choe, Minjeong Kang, Sang-Hyeok Cho, Suhyung Cho, Ki Jun Jeong, Bernhard Palsson, Byung-Kwan Cho
Microbes have inherent capacities for utilizing various carbon sources, however they often exhibit sub-par fitness due to low metabolic efficiency. To test whether a bacterial strain can optimally utilize multiple carbon sources, was serially evolved in L-lactate and glycerol. This yielded two end-point strains that evolved first in L-lactate then in glycerol, and vice versa. The end-point strains
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Efficient production of (S)-limonene and geraniol in Saccharomyces cerevisiae through the utilization of an Erg20 mutant with enhanced GPP accumulation capability Metab. Eng. (IF 6.8) Pub Date : 2024-04-15 Armand Bernard, Seungwoo Cha, Hyesoo Shin, Daeyeol Lee, Ji-Sook Hahn
Monoterpenes and monoterpenoids such as ()-limonene and geraniol are valuable chemicals with a wide range of applications, including cosmetics, pharmaceuticals, and biofuels. has proven to be an effective host to produce various terpenes and terpenoids. ()-limonene and geraniol are produced from geranyl pyrophosphate (GPP) through the enzymatic actions of limonene synthase (LS) and geraniol synthase
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Engineering the cellulolytic bacterium, Clostridium thermocellum, to co-utilize hemicellulose Metab. Eng. (IF 6.8) Pub Date : 2024-04-15 Katherine J. Chou, Trevor Croft, Skyler D. Hebdon, Lauren R. Magnusson, Wei Xiong, Luis H. Reyes, Xiaowen Chen, Emily J. Miller, Danielle M. Riley, Sunnyjoy Dupuis, Kathrin A. Laramore, Lisa M. Keller, Dirk Winkelman, Pin-Ching Maness
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Engineering a solar formic acid/pentose (SFAP) pathway in Escherichia coli for lactic acid production Metab. Eng. (IF 6.8) Pub Date : 2024-04-15 Yajing Zhang, Tao Sun, Linqi Liu, Xupeng Cao, Weiwen Zhang, Wangyin Wang, Can Li
Microbial CO fixation into lactic acid (LA) is an important approach for low-carbon biomanufacturing. Engineering microbes to utilize CO and sugar as co-substrates can create efficient pathways through input of moderate reducing power to drive CO fixation into product. However, to achieve complete conservation of organic carbon, how to engineer the CO-fixing modules compatible with native central metabolism
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Rethinking 13C-metabolic flux analysis – The Bayesian way of flux inference Metab. Eng. (IF 6.8) Pub Date : 2024-04-04 Axel Theorell, Johann F. Jadebeck, Wolfgang Wiechert, Johnjoe McFadden, Katharina Nöh
Metabolic reaction rates (fluxes) play a crucial role in comprehending cellular phenotypes and are essential in areas such as metabolic engineering, biotechnology, and biomedical research. The state-of-the-art technique for estimating fluxes is metabolic flux analysis using isotopic labelling (C-MFA), which uses a dataset-model combination to determine the fluxes. Bayesian statistical methods are gaining
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Combinatorial metabolic engineering of Bacillus subtilis for de novo production of polymyxin B Metab. Eng. (IF 6.8) Pub Date : 2024-04-04 Hui-Zhong Sun, Qing Li, Wei Shang, Bin Qiao, Qiu-Man Xu, Jing-Sheng Cheng
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Resource allocation modeling for autonomous prediction of plant cell phenotypes Metab. Eng. (IF 6.8) Pub Date : 2024-03-30 Anne Goelzer, Loïc Rajjou, Fabien Chardon, Olivier Loudet, Vincent Fromion
Predicting the plant cell response in complex environmental conditions is a challenge in plant biology. Here we developed a resource allocation model of cellular and molecular scale for the leaf photosynthetic cell of , based on the Resource Balance Analysis (RBA) constraint-based modeling framework. The RBA model contains the metabolic network and the major macromolecular processes involved in the
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Nature as blueprint: Global phenotype engineering of CHO production cells based on a multi-omics comparison with plasma cells Metab. Eng. (IF 6.8) Pub Date : 2024-03-30 Nadja Raab, Nikolas Zeh, Robin Kretz, Linus Weiß, Anna Stadermann, Benjamin Lindner, Simon Fischer, Dieter Stoll, Kerstin Otte
Especially for the production of artificial, difficult to express molecules a further development of the CHO production cell line is required to keep pace with the continuously increasing demands. However, the identification of novel targets for cell line engineering to improve CHO cells is a time and cost intensive process. Since plasma cells are evolutionary optimized for a high antibody expression
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Repurposing plant hormone receptors as chemically-inducible genetic switches for dynamic regulation in yeast Metab. Eng. (IF 6.8) Pub Date : 2024-03-29 Shuang Wei, Mengwan Li, Xuye Lang, Nicholas R. Robertson, Sang-Youl Park, Sean R. Cutler, Ian Wheeldon
Precise control of gene expression is critical for optimizing cellular metabolism and improving the production of valuable biochemicals. However, hard-wired approaches to pathway engineering, such as optimizing promoters, can take time and effort. Moreover, limited tools exist for controlling gene regulation in non-conventional hosts. Here, we develop a two-channel chemically-regulated gene expression
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Developing the E. coli platform for efficient production of UMP-derived chemicals Metab. Eng. (IF 6.8) Pub Date : 2024-03-24 Le Yu, Yaojie Gao, Yuanyuan He, Yang Liu, Jianning Shen, Han Liang, Rong Gong, He Duan, Neil P.J. Price, Xuemin Song, Zixin Deng, Wenqing Chen
5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in for the first time, a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly
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Metabolic engineering of Escherichia coli for high-level production of the biodegradable polyester monomer 2-pyrone-4,6-dicarboxylic acid Metab. Eng. (IF 6.8) Pub Date : 2024-03-21 Fengli Wu, Shucai Wang, Dan Zhou, Shukai Gao, Guotian Song, Yanxia Liang, Qinhong Wang
2-Pyrone-4,6-dicarboxylic acid (PDC), a chemically stable pseudo-aromatic dicarboxylic acid, is a promising building block compound for manufacturing biodegradable polyesters. This study aimed to construct high-performance cell factories enabling the efficient production of PDC from glucose. Firstly, the effective enzymes of the PDC biosynthetic pathway were overexpressed on the chromosome of the 3-dehydroshikimate
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Parageobacillus thermoglucosidasius as an emerging thermophilic cell factory Metab. Eng. (IF 6.8) Pub Date : 2024-03-13 Miguel Paredes-Barrada, Panagiotis Kopsiaftis, Nico J. Claassens, Richard van Kranenburg
is a thermophilic and facultatively anaerobic microbe, which is emerging as one of the most promising thermophilic model organisms for metabolic engineering. The use of thermophilic microorganisms for industrial bioprocesses provides the advantages of increased reaction rates and reduced cooling costs for bioreactors compared to their mesophilic counterparts. Moreover, it enables starch or lignocellulose
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Corrigendum to “Cyclo-diphenylalanine Production in Aspergillus nidulans through Stepwise Metabolic Engineering” [Metab. Eng. 82 (2024) 147–156] Metab. Eng. (IF 6.8) Pub Date : 2024-03-11 Xiaolin Liu, Kang Li, Jing Yu, Chuanteng Ma, Qian Che, Tianjiao Zhu, Dehai Li, Blaine A. Pfeifer, Guojian Zhang
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Revealing the dynamics and mechanisms of bacterial interactions in cheese production with metabolic modelling Metab. Eng. (IF 6.8) Pub Date : 2024-03-08 Maxime Lecomte, Wenfan Cao, Julie Aubert, David James Sherman, Hélène Falentin, Clémence Frioux, Simon Labarthe
Cheese taste and flavour properties result from complex metabolic processes occurring in microbial communities. A deeper understanding of such mechanisms makes it possible to improve both industrial production processes and end-product quality through the design of microbial consortia. In this work, we caracterise the metabolism of a three-species community consisting of , and during a seven-week cheese
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Elucidating uptake and metabolic fate of dipeptides in CHO cell cultures using 13C labeling experiments and kinetic modeling Metab. Eng. (IF 6.8) Pub Date : 2024-03-07 Harnish Mukesh Naik, Xiangchen Cai, Pranay Ladiwala, Jayanth Venkatarama Reddy, Michael J. Betenbaugh, Maciek R. Antoniewicz
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Leveraging a Y. lipolytica naringenin chassis for biosynthesis of apigenin and associated glucoside Metab. Eng. (IF 6.8) Pub Date : 2024-03-04 Celeste B. Marsan, Sung Gyung Lee, Ankim Nguyen, Angela R. Gordillo Sierra, Sarah M. Coleman, Sierra M. Brooks, Hal S. Alper
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High titer production of gastrodin enabled by systematic refactoring of yeast genome and an antisense-transcriptional regulation toolkit Metab. Eng. (IF 6.8) Pub Date : 2024-02-28 Yang Gu, Yaru Jiang, Changfan Li, Jiang Zhu, Xueyao Lu, Jianyue Ge, Mengchen Hu, Jieying Deng, Jingbo Ma, Zhiliang Yang, Xiaoman Sun, Feng Xue, Guocheng Du, Peng Xu, He Huang
Gastrodin, a phenolic glycoside, is a prominent component of , which is renowned for its sedative, hypnotic, anticonvulsant, and neuroprotective activities. Engineering heterologous production of plant natural products in microbial host represents a safe, cost-effective, and scalable alternative to plant extraction. Here, we present the construction of an engineered yeast that achieves a high-titer
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High-level production of Rhodiola rosea characteristic component rosavin from D-glucose and L-arabinose in engineered Escherichia coli Metab. Eng. (IF 6.8) Pub Date : 2024-02-28 Lijun Li, Moshi Liu, Huiping Bi, Tao Liu
Rosavin is the characteristic component of L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from
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Genome-wide host-pathway interactions affecting cis-cis-muconic acid production in yeast Metab. Eng. (IF 6.8) Pub Date : 2024-02-28 Paul Cachera, Nikolaj Can Kurt, Andreas Røpke, Tomas Strucko, Uffe H. Mortensen, Michael K. Jensen
The success of forward metabolic engineering depends on a thorough understanding of the behaviour of a heterologous metabolic pathway within its host. We have recently described CRI-SPA, a high-throughput gene editing method enabling the delivery of a metabolic pathway to all strains of the knock-out library. CRI-SPA systematically quantifies the effect of each modified gene present in the library
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Ectoine hyperproduction by engineered Halomonas bluephagenesis Metab. Eng. (IF 6.8) Pub Date : 2024-02-23 Qitiao Hu, Simian Sun, Zhongnan Zhang, Wei Liu, Xueqing Yi, Hongtao He, Nigel S. Scrutton, Guo-Qiang Chen
Ectoine, a crucial osmoprotectant for salt adaptation in halophiles, has gained growing interest in cosmetics and medical industries. However, its production remains challenged by stringent fermentation process in model microorganisms and low production level in its native producers. Here, we systematically engineered the native ectoine producer for ectoine production by overexpressing operon, increasing
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Machine learning predicts system-wide metabolic flux control in cyanobacteria Metab. Eng. (IF 6.8) Pub Date : 2024-02-21 Amit Kugler, Karin Stensjö
Metabolic fluxes and their control mechanisms are fundamental in cellular metabolism, offering insights for the study of biological systems and biotechnological applications. However, quantitative and predictive understanding of controlling biochemical reactions in microbial cell factories, especially at the system level, is limited. In this work, we present ARCTICA, a computational framework that
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Cyclo-diphenylalanine production in Aspergillus nidulans through stepwise metabolic engineering Metab. Eng. (IF 6.8) Pub Date : 2024-02-20 Xiaolin Liu, Kang Li, Jing Yu, Chuanteng Ma, Qian Che, Tianjiao Zhu, Dehai Li, Blaine A. Pfeifer, Guojian Zhang
Cyclo-diphenylalanine (cFF) is a symmetrical aromatic diketopiperazine (DKP) found wide-spread in microbes, plants, and resulting food products. As different bioactivities continue being discovered and relevant food and pharmaceutical applications gradually emerge for cFF, there is a growing need for establishing convenient and efficient methods to access this type of compound. Here, we present a robust
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Combinatorial biosynthesis in yeast leads to over 200 diterpenoids Metab. Eng. (IF 6.8) Pub Date : 2024-02-20 Maximilian Frey, Ulschan Bathe, Luca Meink, Gerd U. Balcke, Jürgen Schmidt, Andrej Frolov, Alena Soboleva, Ahmed Hassanin, Mehdi D. Davari, Oliver Frank, Verena Schlagbauer, Corinna Dawid, Alain Tissier
Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases
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COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling Metab. Eng. (IF 6.8) Pub Date : 2024-02-20 Saratram Gopalakrishnan, William Johnson, Miguel A. Valderrama-Gomez, Elcin Icten, Jasmine Tat, Michael Ingram, Coral Fung Shek, Pik K. Chan, Fabrice Schlegel, Pablo Rolandi, Cleo Kontoravdi, Nathan E. Lewis
Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid
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Reconstructing curcumin biosynthesis in yeast reveals the implication of caffeoyl-shikimate esterase in phenylpropanoid metabolic flux Metab. Eng. (IF 6.8) Pub Date : 2024-02-20 Joseph Christian Utomo, Hailey Brynn Barrell, Rahul Kumar, Jessica Smith, Maximilian Simon Brant, Hector De la Hoz Siegler, Dae-Kyun Ro
Curcumin is a polyphenolic natural product from the roots of turmeric (). It has been a popular coloring and flavoring agent in food industries with known health benefits. The conventional phenylpropanoid pathway is known to proceed from phenylalanine via -coumaroyl-CoA intermediate. Although hydroxycinnamoyl-CoA: shikimate hydroxycinnamoyl transferase (HCT) plays a key catalysis in the biosynthesis
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Metabolic flux optimization of iterative pathways through orthogonal gene expression control: Application to the β-oxidation reversal Metab. Eng. (IF 6.8) Pub Date : 2024-02-20 Seung Hwan Lee, Yang Hu, Alexander Chou, Jing Chen, Ramon Gonzalez
Balancing relative expression of pathway genes to minimize flux bottlenecks and metabolic burden is one of the key challenges in metabolic engineering. This is especially relevant for iterative pathways, such as reverse β-oxidation (rBOX) pathway, which require control of flux partition at multiple nodes to achieve efficient synthesis of target products. Here, we develop a plasmid-based inducible system
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Corynebacterium glutamicum cell factory design for the efficient production of cis, cis-muconic acid Metab. Eng. (IF 6.8) Pub Date : 2024-02-17 Menglei Li, Jiayao Chen, Keqin He, Changsheng Su, Yilu Wu, Tianwei Tan
Cis, -muconic acid (MA) is widely used as a key starting material in the synthesis of diverse polymers. The growing demand in these industries has led to an increased need for MA. Here, we constructed recombinant by systems metabolic engineering, which exhibit high efficiency in the production of MA. Firstly, the three major degradation pathways were disrupted in the MA production process. Subsequently
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Efficient production of protocatechuic acid using systems engineering of Escherichia coli Metab. Eng. (IF 6.8) Pub Date : 2024-02-16 Ming Wang, Haomiao Wang, Cong Gao, Wanqing Wei, Jia Liu, Xiulai Chen, Guipeng Hu, Wei Song, Jing Wu, Fan Zhang, Liming Liu
Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is widely used in the pharmaceuticals, health food, and cosmetics industries owing to its diverse biological activities. However, the inhibition of 3-dehydroshikimate dehydratase (AroZ) by PCA and its toxicity to cells limit the efficient production of PCA in . In this study, a high-level strain of 3-dehydroshikimate, DHS01, was developed by blocking
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Genome-scale and pathway engineering for the sustainable aviation fuel precursor isoprenol production in Pseudomonas putida Metab. Eng. (IF 6.8) Pub Date : 2024-02-16 Deepanwita Banerjee, Ian S. Yunus, Xi Wang, Jinho Kim, Aparajitha Srinivasan, Russel Menchavez, Yan Chen, Jennifer W. Gin, Christopher J. Petzold, Hector Garcia Martin, Jon K. Magnuson, Paul D. Adams, Blake A. Simmons, Aindrila Mukhopadhyay, Joonhoon Kim, Taek Soon Lee
Sustainable aviation fuel (SAF) will significantly impact global warming in the aviation sector, and important SAF targets are emerging. Isoprenol is a precursor for a promising SAF compound DMCO (1,4-dimethylcyclooctane) and has been produced in several engineered microorganisms. Recently, has gained interest as a future host for isoprenol bioproduction as it can utilize carbon sources from inexpensive
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Prediction and integration of metabolite-protein interactions with genome-scale metabolic models Metab. Eng. (IF 6.8) Pub Date : 2024-02-15 Mahdis Habibpour, Zahra Razaghi-Moghadam, Zoran Nikoloski
Metabolites, as small molecules, can act not only as substrates to enzymes, but also as effectors of activity of proteins with different functions, thereby affecting various cellular processes. While several experimental techniques have started to catalogue the metabolite-protein interactions (MPIs) present in different cellular contexts, characterizing the functional relevance of MPIs remains a challenging
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Engineering Saccharomyces cerevisiae for fast vitamin-independent aerobic growth Metab. Eng. (IF 6.8) Pub Date : 2024-02-14 Anja K. Ehrmann, Anna K. Wronska, Thomas Perli, Erik A.F. de Hulster, Marijke A.H. Luttik, Marcel van den Broek, Clara Carqueija Cardoso, Jack T. Pronk, Jean-Marc Daran
Chemically defined media for cultivation of strains are commonly supplemented with a mixture of multiple Class-B vitamins, whose omission leads to strongly reduced growth rates. Fast growth without vitamin supplementation is interesting for industrial applications, as it reduces costs and complexity of medium preparation and may decrease susceptibility to contamination by auxotrophic microbes. In this
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KETCHUP: Parameterizing of large-scale kinetic models using multiple datasets with different reference states Metab. Eng. (IF 6.8) Pub Date : 2024-02-07 Mengqi Hu, Patrick F. Suthers, Costas D. Maranas
Large-scale kinetic models provide the computational means to dynamically link metabolic reaction fluxes to metabolite concentrations and enzyme levels while also conforming to substrate level regulation. However, the development of broadly applicable frameworks for efficiently and robustly parameterizing models remains a challenge. Challenges arise due to both the heterogeneity, paucity, and difficulty
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Engineering mammalian cell growth dynamics for biomanufacturing Metab. Eng. (IF 6.8) Pub Date : 2024-02-06 Mauro Torres, Dewi Mcconnaughie, Samia Akhtar, Claire E. Gaffney, Bruno Fievet, Catherine Ingham, Mark Stockdale, Alan J. Dickson
Precise control over mammalian cell growth dynamics poses a major challenge in biopharmaceutical manufacturing. Here, we present a multi-level cell engineering strategy for the tunable regulation of growth phases in mammalian cells. Initially, we engineered mammalian death phase by employing CRISPR/Cas9 to knockout pro-apoptotic proteins Bax and Bak, resulting in a substantial attenuation of apoptosis
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Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids Metab. Eng. (IF 6.8) Pub Date : 2024-02-05 Genlai Dong, Ying Zhao, Wentao Ding, Shijie Xu, Qi Zhang, Huimin Zhao, Shuobo Shi
Odd-numbered fatty acids (FAs) have been widely used in nutrition, agriculture, and chemical industries. Recently, some studies showed that they could be produced from bacteria or yeast, but the products are almost exclusively odd-numbered long-chain FAs. Here we report the design and construction of two biosynthetic pathways in for production of odd-numbered medium-chain fatty acids (OMFAs) via ricinoleic
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A self-regulated network for dynamically balancing multiple precursors in complex biosynthetic pathways Metab. Eng. (IF 6.8) Pub Date : 2024-02-03 Yusong Zou, Jianli Zhang, Jian Wang, Xinyu Gong, Tian Jiang, Yajun Yan
Microbial synthesis has emerged as a promising and sustainable alternative to traditional chemical synthesis and plant extraction. However, the competition between synthetic pathways and central metabolic pathways for cellular resources may impair final production efficiency. Moreover, when the synthesis of target product requires multiple precursors from the same node, the conflicts of carbon flux
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LipidSIM: Inferring mechanistic lipid biosynthesis perturbations from lipidomics with a flexible, low-parameter, Markov modeling framework Metab. Eng. (IF 6.8) Pub Date : 2024-02-02 Chenguang Liang, Sue Murray, Yang Li, Richard Lee, Audrey Low, Shruti Sasaki, Austin W.T. Chiang, Wen-Jen Lin, Joel Mathews, Will Barnes, Nathan E. Lewis
Lipid metabolism is a complex and dynamic system involving numerous enzymes at the junction of multiple metabolic pathways. Disruption of these pathways leads to systematic dyslipidemia, a hallmark of many pathological developments, such as nonalcoholic steatohepatitis and diabetes. Recent advances in computational tools can provide insights into the dysregulation of lipid biosynthesis, but limitations
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Cross-regulation between proteome reallocation and metabolic flux redistribution governs bacterial growth transition kinetics Metab. Eng. (IF 6.8) Pub Date : 2024-02-02 Huili Yuan, Yang Bai, Xuefei Li, Xiongfei Fu
Bacteria need to adjust their metabolism and protein synthesis simultaneously to adapt to changing nutrient conditions. It’s still a grand challenge to predict how cells coordinate such adaptation due to the cross-regulation between the metabolic fluxes and the protein synthesis. Here we developed a dynamic Constrained Allocation Flux Balance Analysis method (dCAFBA), which integrates flux-controlled
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Evaluation of enzyme-constrained genome-scale model through metabolic engineering of anaerobic co-production of 2,3-butanediol and glycerol by Saccharomyces cerevisiae Metab. Eng. (IF 6.8) Pub Date : 2024-02-01 Gustav Sjöberg, Alīna Reķēna, Matilda Fornstad, Petri-Jaan Lahtvee, Antonius J.A. van Maris
Enzyme-constrained genome-scale models (ecGEMs) have potential to predict phenotypes in a variety of conditions, such as growth rates or carbon sources. This study investigated if ecGEMs can guide metabolic engineering efforts to swap anaerobic redox-neutral ATP-providing pathways in yeast from alcoholic fermentation to equimolar co-production of 2,3-butanediol and glycerol. With proven pathways and
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Expression in CHO cells of a bacterial biosynthetic pathway producing a small non-ribosomal peptide aldehyde prevents proteolysis of recombinant proteins Metab. Eng. (IF 6.8) Pub Date : 2024-01-28 Violeta Guadarrama-Pérez, César Aguilar, Alberto Porras-Sanjuanico, Enrique Merino, Octavio T. Ramírez, Francisco Barona-Gómez, Laura A. Palomares
A significant problem during recombinant protein production is proteolysis. One of the most common preventive strategies is the addition of protease inhibitors, which has drawbacks, such as their short half-life and high cost, and their limited prevention of extracellular proteolysis. Actinomycetes produce the most commonly used inhibitors, which are non-ribosomal small aldehydic peptides. Previously
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Corrigendum to “Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells” [Metabol. Eng. 45 (2018) 149–157] Metab. Eng. (IF 6.8) Pub Date : 2024-01-19 Emanuel Gonçalves, Marco Sciacovelli, Ana S.H. Costa, Maxine Gia Binh Tran, Timothy Isaac Johnson, Daniel Machado, Christian Frezza, Julio Saez-Rodriguez
Abstract not available
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YaliCMulti and YaliHMulti: Stable, efficient multi-copy integration tools for engineering Yarrowia lipolytica Metab. Eng. (IF 6.8) Pub Date : 2024-01-14 Mengsu Liu, Junjun Wu, Mingyu Yue, Yang Ning, Xin Guan, Song Gao, Jingwen Zhou
is widely used in biotechnology to produce recombinant proteins, food ingredients and diverse natural products. However, unstable expression of plasmids, difficult and time-consuming integration of single and low-copy-number plasmids hampers the construction of efficient production pathways and application to industrial production. Here, by exploiting sequence diversity in the long terminal repeats
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Consistent biosynthesis of D-glycerate from variable mixed substrates Metab. Eng. (IF 6.8) Pub Date : 2024-01-05 Cynthia Ni, Kristala L.J. Prather
The use of waste streams and other renewable feedstocks in microbial biosynthesis has long been a goal for metabolic engineers. Microbes can utilize the substrate mixtures found in waste streams, though they are more technically challenging to convert to useful products compared to the single substrates of standard practice. It is difficult to achieve consistent biosynthesis in the face of the temporally
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Enhanced poly-γ-glutamic acid synthesis in Corynebacterium glutamicum by reconstituting PgsBCA complex and fermentation optimization Metab. Eng. (IF 6.8) Pub Date : 2023-12-29 Guoqiang Xu, Jiyue Wang, Jiancheng Shen, Yaxin Zhu, Wanjing Liu, Yuhang Chen, Jian Zha, Xiaomei Zhang, Xiaojuan Zhang, Jinsong Shi, Mattheos A.G. Koffas, Zhenghong Xu
Previously, a novel Corynebacterium glutamicum strain for the de novo biosynthesis of tailored poly-γ-glutamic acid (γ-PGA) has been constructed by our group. The strain was based on the γ-PGA synthetase complex, PgsBCA, which is the only polyprotein complex responsible for γ-PGA synthesis in Bacillus spp. In the present study, PgsBCA was reconstituted and overexpressed in C. glutamicum to further
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Creating new-to-nature carbon fixation: A guide Metab. Eng. (IF 6.8) Pub Date : 2023-12-29 Helena Schulz-Mirbach, Beau Dronsella, Hai He, Tobias J. Erb
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Flux optimization using multiple promoters in Halomonas bluephagenesis as a model chassis of the next generation industrial biotechnology Metab. Eng. (IF 6.8) Pub Date : 2023-12-28 Yueyuan Ma, Jian-Wen Ye, Yina Lin, Xueqing Yi, Xuan Wang, Huan Wang, Ruiyan Huang, Fuqing Wu, Qiong Wu, Xu Liu, Guo-Qiang Chen
Predictability and robustness are challenges for bioproduction because of the unstable intracellular synthetic activities. With the deeper understanding of the gene expression process, fine-tuning has become a meaningful tool for biosynthesis optimization. This study characterized several gene expression elements and constructed a multiple inducible system that responds to ten different small chemical