Metabolic engineering最新文献

{"title":"Engineering phenylpyruvate decarboxylase for controlled biosynthesis of aromatic amino acid derivatives","authors":"Jian Li ,&nbsp;Shiqing Zhang ,&nbsp;Honghao Li ,&nbsp;Xiaoran Dai ,&nbsp;Chaoqun Huang ,&nbsp;He Ma ,&nbsp;Huayi Liu ,&nbsp;Qi Qi ,&nbsp;Xiang Sheng ,&nbsp;Yunzi Luo","doi":"10.1016/j.ymben.2025.07.001","DOIUrl":"10.1016/j.ymben.2025.07.001","url":null,"abstract":"<div><div>The biosynthetic pathway of aromatic amino acids (AAAs) and its branches are crucial for producing bioactive compounds. ARO10, a phenylpyruvate decarboxylase in yeast, catalyzes the decarboxylation of 2-keto acids to aldehydes, playing a key role in AAA-derivative biosynthesis in yeast. However, its broad substrate specificity hinders efficient target synthesis. Here, we engineered ARO10 to create three mutants (I335E, A628F/H339I/I335M, H339C/I335T/A628Q) with specificity for 4-hydroxyphenylpyruvic acid (4-HPP), phenylpyruvic acid (PPA), and indole-3-pyruvic acid (I3P) through a “Design-Build-Test-Learn” (DBTL) framework. Mechanisms were explored via enzyme kinetics and molecular dynamics. These mutants enabled high-yield production of AAA-derivatives in yeast strains: 11.08 g/L tyrosol, 2.77 g/L 2-phenylethanol, and 1.21 g/L tryptophol in 5 L fed-batch bioreactor. These are the highest reported <em>de novo</em> titers to date in yeast. This work highlights the potential for engineering promiscuous enzymes to enhance sustainable biosynthesis of AAA-derivatives and alkaloids.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 466-479"},"PeriodicalIF":6.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring Escherichia coli for high-yield production of O-acetyl-L-homoserine through multi-node metabolic regulation","authors":"Yuanyuan Chen ,&nbsp;Lianggang Huang ,&nbsp;Tao Yu ,&nbsp;Mingming Zhao ,&nbsp;Junping Zhou ,&nbsp;Lijuan Wang ,&nbsp;Zhiqiang Liu ,&nbsp;Yuguo Zheng","doi":"10.1016/j.ymben.2025.06.010","DOIUrl":"10.1016/j.ymben.2025.06.010","url":null,"abstract":"<div><div>O-acetyl-L-homoserine (OAH) is a key precursor for the biosynthesis of L-methionine and various C4 compounds, with significant industrial potential. However, efficient microbial production of OAH remains challenging due to complex metabolic regulation and precursor limitations. In this study, we rationally developed a plasmid-free, non-auxotrophic <em>Escherichia coli</em> strain to produce OAH. We modularized the OAH synthetic pathway into L-homoserine and acetyl-CoA modules, enhanced each module individually, and identified a highly efficient L-homoserine O-acetyltransferase (MetX) from <em>Cyclobacterium marinum</em>. Using small RNA screening, we pinpointed critical metabolic nodes and fine-tuned the pathway flux through promoter engineering and regulatory elements. Notably, we balanced the acetyl-CoA and L-homoserine synthesis with moderate expression of pyruvate carboxylase, weakened the TCA cycle by modulating citrate synthase and the branched-chain amino acid pathway by attenuating BCAA aminotransferase, thereby redirecting carbon flux towards OAH production. Additionally, we optimized the threonine attenuator for dynamic regulation of the threonine pathway and enhanced intracellular ATP turnover. Under a two-stage pH control fermentation strategy, the final plasmid-free and non-auxotrophic strain OAH37 achieved a titer of 94.1 g/L OAH, with a yield of 0.42 g/g glucose and a productivity of 1.37 g/L/h. Our work demonstrates the potential of metabolic engineering strategies for efficient microbial synthesis of OAH, providing a foundation for industrial-scale production of this important precursor.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 455-465"},"PeriodicalIF":6.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multilayered biocontainment system for laboratory and probiotic yeast","authors":"Carla Maneira ,&nbsp;Sina Becker ,&nbsp;Alexandre Chamas ,&nbsp;Gerald Lackner","doi":"10.1016/j.ymben.2025.06.009","DOIUrl":"10.1016/j.ymben.2025.06.009","url":null,"abstract":"<div><div>The containment of genetically engineered microorganisms to designated environments of action is a paramount step in preventing their spread to nature. Physical barriers were traditionally employed to solve this issue, nevertheless, the growing number of biotechnological operations in open dynamic environments calls for intrinsic biocontainment. Here we describe the development of genetically embedded safeguard systems for both a laboratory strain of <em>Saccharomyces cerevisiae</em> and the commercial probiotic <em>Saccharomyces cerevisiae</em> var. <em>boulardii</em>. In a stepwise approach, single-input metabolic circuits based either on a synthetic auxotrophy or a CRISPR-based kill switch were developed before their combination into an orthogonal two-input system. All circuits are based on gut-active molecules or environmental cues, making them amenable to microbiome therapy applications. The final two-input system is stable for more than a hundred generations while achieving less than one escapee in 10⁹ CFUs after incubation under restrictive conditions for at least six days. Biocontained strains can robustly produce heterologous proteins under permissive conditions, supporting their future use in the most varied applications, like <em>in-situ</em> production and delivery of pharmaceutically active metabolites.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 442-454"},"PeriodicalIF":6.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production","authors":"Bharath Narayanan ,&nbsp;Wei Jiang ,&nbsp;Shengbao Wang ,&nbsp;Javier Sáez-Sáez ,&nbsp;Daniel Weilandt ,&nbsp;Maria Masid Barcon ,&nbsp;Viktor Hesselberg-Thomsen ,&nbsp;Irina Borodina ,&nbsp;Vassily Hatzimanikatis ,&nbsp;Ljubisa Miskovic","doi":"10.1016/j.ymben.2025.06.008","DOIUrl":"10.1016/j.ymben.2025.06.008","url":null,"abstract":"<div><div>The use of kinetic models of metabolism in design-build-learn-test cycles is limited despite their potential to guide and accelerate the optimization of cell factories. This is primarily due to difficulties in constructing kinetic models capable of capturing the complexities of the fermentation conditions. Building on recent advances in kinetic-model-based strain design, we present the rational metabolic engineering of an <em>S. cerevisiae</em> strain designed to overproduce <em>p</em>-coumaric acid (<em>p</em>-CA), an aromatic amino acid with valuable nutritional and therapeutic applications. To this end, we built nine kinetic models of an already engineered <em>p</em>-CA-producing strain by integrating different types of omics data and imposing physiological constraints pertinent to the strain. These nine models contained 268 mass balances involved in 303 reactions across four compartments and could reproduce the dynamic characteristics of the strain in batch fermentation simulations. We used constraint-based metabolic control analysis to generate combinatorial designs of 3 enzyme manipulations that could increase p-CA yield on glucose while ensuring that the resulting engineering strains did not deviate far from the reference phenotype. Among 39 unique designs, 10 proved robust across the phenotypic uncertainty of the models and could reliably increase <em>p</em>-CA yield in nonlinear simulations. We implemented these top 10 designs in a batch fermentation setting using a promoter-swapping strategy for down-regulations and plasmids for up-regulations. Eight out of the ten designs produced higher <em>p</em>-CA titers than the reference strain, with 19–32 % increases at the end of fermentation. All eight designs also maintained at least 90 % of the reference strain's growth rate, indicating the critical role of the phenotypic constraint. The high experimental success of our in-silico predictions lays the foundation for accelerated design-build-test-learn cycles enabled by large-scale kinetic modeling.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 430-441"},"PeriodicalIF":6.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling host–pathway dynamics at the genome scale with machine learning","authors":"Charlotte Merzbacher ,&nbsp;Oisin Mac Aodha ,&nbsp;Diego A. Oyarzún","doi":"10.1016/j.ymben.2025.05.008","DOIUrl":"10.1016/j.ymben.2025.05.008","url":null,"abstract":"<div><div>Pathway engineering offers a promising avenue for sustainable chemical production. The design of efficient production systems requires understanding complex host–pathway interactions that shape the metabolic phenotype. While genome-scale metabolic models are widespread tools for studying static host–pathway interactions, it remains a challenge to predict dynamic effects such as metabolite accumulation or enzyme overexpression during the course of fermentation. Here, we propose a novel strategy to integrate kinetic pathway models with genome-scale metabolic models of the production host. Our method enables the simulation of the local nonlinear dynamics of pathway enzymes and metabolites, informed by the global metabolic state of the host as predicted by Flux Balance Analysis (FBA). To reduce computational costs, we make extensive use of surrogate machine learning models to replace FBA calculations, achieving simulation speed-ups of at least two orders of magnitude. Through case studies on two production pathways in <em>Escherichia coli</em>, we demonstrate the consistency of our simulations and the ability to predict metabolite dynamics under genetic perturbations and various carbon sources. We showcase the utility of our method for screening dynamic control circuits through large-scale parameter sampling and mixed-integer optimization. Our work links together genome-scale and kinetic models into a comprehensive framework for computational strain design.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 480-491"},"PeriodicalIF":6.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering genetic circuits for dynamic control of central metabolism","authors":"Yusong Zou,&nbsp;Xinyu Gong,&nbsp;Jianli Zhang,&nbsp;Qi Gan,&nbsp;Yajun Yan","doi":"10.1016/j.ymben.2025.06.007","DOIUrl":"10.1016/j.ymben.2025.06.007","url":null,"abstract":"<div><div>Genetic regulation tools have been examined for their ability to enable sophisticated dynamic control of biosynthesis in microbial cell factories, enhancing the production performance of valuable compounds. However, most genetic tools are pathway- or intermediate-specific, hindering their broad applicability in synthetic biology. Moreover, their potential to balance metabolic fluxes in central metabolism between cell growth and product formation remains under-explored, raising the question of whether they can facilitate efficient biosynthesis. To answer this, we established the PdhR biosensor system that responds to pyruvate to dynamically regulate metabolic flux distribution in central metabolism. In this study, we first characterized the dose response of PdhR biosensor system by screening multiple PdhR homologs derived from various microorganisms. Computational analysis further guided the identification of key factors contributing to their functional differences, enabling the optimization of biosensor properties through site-directed mutagenesis. As proof of concept, we employed our biosensor system to improve the biosynthesis of trehalose and 4-hydroxycoumarin (4HC), respectively. Specifically, trehalose titer increased to 3.72 g/L, which is 2.33-fold higher than the control group. In addition, we improved the 4HC titer to 491.5 mg/L, which possessed a 1.63-fold increase over the static strategy. In summary, the established central metabolism-responsive biosensor system underlined the necessity of metabolic flux distribution and validated its broad applicability in the biosynthesis of central metabolism-derived compounds.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 405-414"},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering of Escherichia coli cytoplasm and periplasm for efficient synthesis of salvianic acid A","authors":"Daoguang Tian ,&nbsp;Guifeng Tian ,&nbsp;Zhen Qin ,&nbsp;Shengli Wang ,&nbsp;Shengbo Wu ,&nbsp;Peng Zhang ,&nbsp;Bo Xiong ,&nbsp;Mingyue Ge ,&nbsp;Juane Lu ,&nbsp;Weiguo Li ,&nbsp;Guang-Rong Zhao ,&nbsp;Jianjun Qiao","doi":"10.1016/j.ymben.2025.06.006","DOIUrl":"10.1016/j.ymben.2025.06.006","url":null,"abstract":"<div><div>Plant polyphenols, a class of natural plant products with nutritional and medicinal value, can be alternatively produced by microbial cell factories. However, metabolic cross talk and enzyme incompatibility within the microbial host limits their synthesis. Therefore, we developed a sustainability-driven biotechnological process using cytoplasm periplasm combinatorial engineering to producing salvianic acid A (SAA), a plant polyphenol derived from the roots of <em>Salvia miltiorrhiza</em>. SAA possesses potent cardiovascular and therapeutic benefits, but its rising demand is constrained by limited natural yields. First, we optimized an artificial SAA pathway by identifying an efficient 4-hydroxyphenyllatic acid dehydrogenase and 4-hydroxyphenyllatic acid hydroxylase, followed by improving the catalytic performance of hydroxylase. Periplasm engineering further enhanced SAA synthesis while reducing by-product formation. Additionally, cofactor engineering was applied to ensure an adequate supply of both periplasmic and cytoplasmic cofactors. The resulting strain was capable of producing up to 37.26 g L⁻¹ of SAA, a new record in engineered microbial performance. The strategy reported here can be used for the large-scale production of other plant polyphenols and natural products.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 415-429"},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic engineering in Hot Acid: Strategies enabling chemolithotrophy in thermoacidophilic archaea","authors":"Daniel J. Willard ,&nbsp;Robert M. Kelly","doi":"10.1016/j.ymben.2025.06.005","DOIUrl":"10.1016/j.ymben.2025.06.005","url":null,"abstract":"<div><div>A genome-scale metabolic model was developed to explore metabolic engineering strategies for thermoacidophilic archaea, with a focus on the genetically tractable <em>Sulfolobus acidocaldarius</em> (T_opt 75 °C, pH_opt 2.5). <em>S. acidocaldarius</em> is natively neither an autotroph nor a sulfur oxidizer, although its genome suggests that this might have been the case at some evolutionary point. Comparative genomics provided insights into key genes and pathways missing from <em>S. acidocaldarius</em> necessary for chemolithotrophy. Growth data for the chemolithotrophic sulfur oxidizer, <em>Sulfurisphaera ohwakuensis</em> (T_opt 85 °C, pH_opt 2.0), provided metabolic data to inform model development. Previous metabolic engineering efforts enabled sulfur oxidation by <em>S. acidocaldarius</em>, albeit at levels below native sulfur oxidizers. Model analysis pointed to active sulfur transport as a key missing complement to passive diffusion. Modelling results predicted that sulfur oxidation could drive production of a bio-based chemical, acetone, in engineered strains of <em>S. acidocaldarius</em> with concomitant fixation of CO₂ into product via the 3-Hydroxybutyrate/4-Hydroxybutyrate cycle. The findings here provide new insights into the basis for thermoacidophile chemolithotrophy and motivate further efforts to develop <em>S. acidocaldarius</em> into a valuable metabolic engineering platform.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 366-378"},"PeriodicalIF":6.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems-level analysis provides insights on methanol-based production of l-glutamate and its decarboxylation product γ-aminobutyric acid by Bacillus methanolicus","authors":"Marta Irla ,&nbsp;Ingemar Nærdal ,&nbsp;David Virant ,&nbsp;Trygve Brautaset ,&nbsp;Tobias Busche ,&nbsp;Dušan Goranovič ,&nbsp;Carsten Haupka ,&nbsp;Stéphanie Heux ,&nbsp;Gregor Kosec ,&nbsp;Christian Rückert-Reed ,&nbsp;Volker F. Wendisch ,&nbsp;Luciana F. Brito ,&nbsp;Cláudia M. Vicente","doi":"10.1016/j.ymben.2025.06.002","DOIUrl":"10.1016/j.ymben.2025.06.002","url":null,"abstract":"<div><div><em>Bacillus methanolicus</em> is the next workhorse in biotechnology using methanol, an alternative and economical one-carbon feedstock that can be obtained directly from carbon dioxide, as both carbon and energy source for the production of value-added chemicals. The wild-type strain <em>B. methanolicus</em> MGA3 naturally overproduces <span>l</span>-glutamate in methanol-based fed-batch fermentations. Here we generated a <em>B. methanolicus</em> strain exhibiting enhanced <span>l</span>-glutamate production capability through induced mutagenesis. To showcase the potential of this mutant strain, further metabolic engineering enabled the production of γ-aminobutyric acid (GABA) directly from <span>l</span>-glutamate during methanol fed-batch fermentations. Using a systems-level analysis, encompassing whole-genome sequencing, RNA sequencing, fluxome analysis and genome-scale metabolic modelling, we were able to elucidate the metabolic and regulatory adaptations that sustain the biosynthesis of these products. The metabolism of the mutant strain specifically evolved to prioritize energy conservation and efficient carbon utilization, culminating in increased product formation. These results and insights provide a foundation for further rational metabolic engineering and bioprocess optimization, enhancing the industrial viability of <em>B. methanolicus</em> for sustainable production of <span>l</span>-glutamate and its derivatives.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 389-404"},"PeriodicalIF":6.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High glutamate demand enables simultaneous consumption of glycerol and citrate despite carbon catabolite repression in engineered Bacillus subtilis strains","authors":"Frederik Völker ,&nbsp;Sandra Maaß ,&nbsp;An N.T. Phan ,&nbsp;Johannes Gibhardt ,&nbsp;Fabian M. Commichau ,&nbsp;Lars M. Blank","doi":"10.1016/j.ymben.2025.06.003","DOIUrl":"10.1016/j.ymben.2025.06.003","url":null,"abstract":"<div><div>The increasing demand for biopolymers has positioned poly-γ-glutamic acid (γ-PGA) as a promising alternative to fossil-based polymers due to its biodegradability and biocompatibility. γ-PGA biosynthesis in <em>Bacillus subtilis</em> is closely linked to intracellular glutamate availability, which is typically maintained via the supply of an exogenous glutamate source, a cost-intensive factor for industrial production. This study investigates the metabolic interplay between glycerol, citrate, and glutamate during γ-PGA synthesis, focusing on how cellular glutamate demand influences carbon source utilization. We demonstrate that reducing exogenous glutamate supply induces demand-driven co-consumption of glycerol and citrate, which is usually inhibited by carbon catabolite repression. In the absence of exogenous glutamate, the <em>B. subtilis</em> strain PG10 produced 8.4 g L⁻¹ γ-PGA, indicating significant <em>de novo</em> glutamate synthesis. A deletion analysis of known citrate transporters identified CimH as the key translocation system enabling citrate uptake under glutamate-limiting conditions. Further isotope labeling confirmed that citrate serves as a glutamate precursor during glutamate demand and is not used as a gluconeogenic substrate. Proteome analysis revealed a regulatory shift towards enhanced glutamate biosynthesis in the absence of exogenous glutamate, accompanied by reduced overflow metabolism and adaptive changes in central carbon and nitrogen metabolism. To our knowledge, carbon source co-utilization is a so far unknown response of <em>B. subtilis</em> 168 to glutamate scarcity. Uncovering the regulatory network involved offers a powerful tool by enabling biotechnological exploitation of this drastic change in carbon flux to boost the production of various products dependent on tricarboxylic acid cycle intermediates.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 379-388"},"PeriodicalIF":6.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}