Metabolic engineering最新文献

{"title":"MDG1-mediated transcriptional reprogramming enhances cellulase production and alters thermal activity in recombinant Saccharomyces cerevisiae","authors":"Chun Wan ,&nbsp;Xue-Qing Wang ,&nbsp;Hou-Ru Yue ,&nbsp;Ming-Ming Zhang ,&nbsp;Akihiko Kondo ,&nbsp;Riaan den Haan ,&nbsp;Tomohisa Hasunuma ,&nbsp;Kai Li ,&nbsp;Xin-Qing Zhao","doi":"10.1016/j.ymben.2025.09.002","DOIUrl":"10.1016/j.ymben.2025.09.002","url":null,"abstract":"<div><div>The budding yeast <em>Saccharomyces cerevisiae</em> is one of the most widely used microbial cell factories for heterologous protein and enzyme production. However, improving production efficiency and tailoring enzyme properties remain a major challenge. Here we identified <em>MDG1</em>, a gene involved in the pheromone signaling pathway, as a previously unrecognized regulator that significantly enhances cellulase production in recombinant yeast. Overexpression of <em>MDG1</em> significantly increased the extracellular activities of β-glucosidase I (BGLI), cellobiohydrolase I (CBHI), and endo-glycosidase II (EGII). Intriguingly, <em>MDG1</em> overexpression also altered the thermal activity profile of BGLI, shifting its peak activity from 50 °C to 37 °C—an inversion relative to the parental strain. Integrated transcriptome analyses revealed that <em>MDG1</em> regulates the expression of genes involved in the cell cycle and protein folding. Targeted modulation of key cell cycle regulators (<em>CLN1, PCL1, SWI5</em>) further improved BGLI activity, confirming their functional involvement. Secretome analysis and functional assays identified the disulfide isomerase Pdi1p as a key contributor to the enhanced enzyme performance at 37 °C. Our study reveals a novel role of <em>MDG1</em> in coordinating gene networks to improve enzyme activities and reshape enzymatic properties.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"93 ","pages":"Pages 24-34"},"PeriodicalIF":6.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035700","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":"Reconstruction of a resource balance analysis model of Clostridium thermocellum examines the metabolic cost of glycolytic and cellulosome enzymes","authors":"Thomas C. Willis ,&nbsp;Wheaton L. Schroeder ,&nbsp;Daven B. Khana ,&nbsp;Xuejun Qian ,&nbsp;Sanjeev Dahal ,&nbsp;Daniel Amador-Noguez ,&nbsp;Costas D. Maranas","doi":"10.1016/j.ymben.2025.09.001","DOIUrl":"10.1016/j.ymben.2025.09.001","url":null,"abstract":"<div><div><em>Clostridium thermocellum</em> is an increasingly well-studied organism with considerable advantages for consolidated bioprocessing towards ethanol production. Here, a genome-scale resource balance analysis (RBA) model of <em>C. thermocellum</em>, ctRBA, is reconstructed based on a recently published stoichiometric model (<em>i</em>CTH669), global proteomics, and ¹³C MFA datasets to analyze proteome allocation and the burden imposed on metabolism with regard to ethanol yield and titer. Glycolytic and fermentation enzyme concentrations were accurately quantified by the model, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and acetaldehyde-alcohol dehydrogenase (AdhE) having predicted and measured higher concentrations relative to other enzymes in glycolysis and fermentation. The metabolic burden associated with the formation of the cellulosome, the enzyme complex responsible for carbon source degradation and solubilization, was assessed and found to be consequential in constraining ethanol yield and titer, but not biomass formation. Putative enzyme substitution strains were modeled, with each strain replacing a single enzyme in <em>C. thermocellum</em> with a variant that uses more favorable cofactors. Strains substituting GAPDH and phosphofructokinase (PFK) predicted 30 % and 86 % increases in maximum theoretical ethanol yield and titer, respectively, a result unavailable to typical stoichiometric modeling. Model ctRBA acts as a predictive tool for assessing the effect of genetic perturbations on proteome allocation and ethanol yield and titer.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"93 ","pages":"Pages 14-23"},"PeriodicalIF":6.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031857","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 metabolic engineering of Klebsiella pneumoniae for high-level 1,3-propanediol production","authors":"Shaolun Zhang ,&nbsp;Fan Zhang ,&nbsp;Jiake Sun ,&nbsp;Hailang Yu ,&nbsp;Peng Sun ,&nbsp;Jia Liu ,&nbsp;Xiaomin Li ,&nbsp;Guipeng Hu ,&nbsp;Jing Wu ,&nbsp;Cong Gao ,&nbsp;Liming Liu","doi":"10.1016/j.ymben.2025.08.012","DOIUrl":"10.1016/j.ymben.2025.08.012","url":null,"abstract":"<div><div>1,3-Propanediol (1,3-PDO) is an essential monomer used in the synthesis of polytrimethylene terephthalates. However, the microbial production of 1,3-PDO is limited by product tolerance and Vitamin B12 (VB₁₂) supplementation. In this study, FMME-KP—a <em>Klebsiella pneumoniae</em> strain with a 1,3-PDO titer of 63.4 g/L. Through pathway reprogramming, the 1,3-PDO titer of strain FMME-14 was increased by 49.1 %. To enhance strain tolerance, a 1,3-PDO biosensor was developed to screen for high-yield strains during adaptive laboratory evolution. Reverse metabolic engineering of genes <em>ydaM</em>^L63V and <em>pgaD</em> improved the 1,3-PDO tolerance of strain FMME-38 by 62.5 %, leading to a 15.9 % increase in 1,3-PDO production. By enhancing the supply of cofactors VB₁₂ and NADH, strain FMME-51 produced 138.6 g/L 1,3-PDO, with a yield of 0.52 g/g within 48 h, without the need for external VB₁₂ supplementation. Additionally, this strain produced 122.7 g/L of 1,3-PDO using crude glycerol as a substrate. To the best of our knowledge, this is the highest reported titer and yield of microbial 1,3-PDO production.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"93 ","pages":"Pages 1-13"},"PeriodicalIF":6.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960300","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":"Biosynthesis of 2,5-pyridinedicarboxylate from glucose via p-aminobenzoic acid in Escherichia coli","authors":"Akinobu Katano ,&nbsp;Ayana Mori ,&nbsp;Daisuke Nonaka ,&nbsp;Yutaro Mori ,&nbsp;Shuhei Noda ,&nbsp;Tsutomu Tanaka","doi":"10.1016/j.ymben.2025.08.011","DOIUrl":"10.1016/j.ymben.2025.08.011","url":null,"abstract":"<div><div>Pyridine carboxylic acids, because of their structural similarity to aromatic carboxylic acids, have garnered increasing attention as alternative compounds in chemical synthesis. However, their broader utilization has been limited by challenges in biosynthetic production. In this study, we developed a metabolic pathway for biosynthesizing 2,5-pyridinedicarboxylate (2,5-PDCA) from glucose from <em>p</em>-aminobenzoate (PABA). The heterologous expression of 4-amino-3-hydroxybenzoate 2,3-dioxygenase (AhdA) in <em>Escherichia coli</em> enabled the conversion of 0.5 g/L of 4-amino-3-hydroxybenzoate (4A3HBA) into 0.47 g/L of 2,5-PDCA. Subsequent systematic evaluation of <em>p</em>-hydroxybenzoate hydroxylase (PobA) variants and optimization of <em>pobA</em> and <em>ahdA</em> co-expression facilitated the development of a 2,5-PDCA biosynthetic module for efficient production from PABA. Incorporating this module into a PABA biosynthesis pathway enabled direct 2,5-PDCA production from glucose. Further enhancements were achieved by increasing metabolic flux through the shikimate pathway and optimizing sodium pyruvate supplementation. Under optimized conditions, we achieved a titer of 1.84 g/L in test-tube cultures after 72 h and 10.6 g/L in bioreactor fermentation after 144 h. Overall, this study introduces a valuable strategy for the microbial production of pyridine carboxylates and establishes a promising platform for broader applications in aromatic compound biosynthesis.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 252-261"},"PeriodicalIF":6.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908973","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 metabolic engineering strategy for producing poly-(3-hydroxyoctanoic acid) in Escherichia coli from glycerol","authors":"Shivangi Mishra,&nbsp;Ke Xu,&nbsp;Madeline K. Kuckuk,&nbsp;William T. Cordell,&nbsp;Néstor J. Hernández-Lozada,&nbsp;Brian F. Pfleger","doi":"10.1016/j.ymben.2025.08.009","DOIUrl":"10.1016/j.ymben.2025.08.009","url":null,"abstract":"<div><div>Poly(3-hydroxyoctanoate) (PHO) is a medium-chain-length PHA with low crystallinity and high elongation to break ratio, unlike the brittle short-chain-PHAs like PHB. These properties make PHO a promising candidate for industrial and biomedical applications. In this study, we demonstrated the production of PHO in <em>Escherichia coli</em> from a renewable and inexpensive glycerol feedstock by engineering fatty acid synthesis and β-oxidation to create a pool of 2,3-octenoyl-CoAs. In this base strain, <em>E. coli</em> Δ<em>fadRABIJ,</em> an (R)-specific enoyl-CoA hydratase (<em>phaJ</em>) and a PHA synthase (<em>phaC</em>) were expressed to produce PHO. Bioprospecting <em>phaJ</em> and <em>phaC</em> homologs from <em>Pseudomonas aeruginosa</em> and <em>fadD</em> homolog from <em>Pseudomonas putida</em> implicated a combination of <em>phaJ2</em>, <em>phaC2</em>, and ^Pp<em>fadD</em> genes yielded the highest PHO content from exogenously fed octanoate. Finally, when a single copy of a previously described C₈-specific thioesterase mutant <em>CpFatB1.2-M4-287</em> was integrated into the chromosome of <em>E. coli</em> Δ<em>fadRABIJ,</em> the resulting <em>E. coli</em> strain NHL18 was capable of producing 3.69 ± 0.146 g/L of octanoic acid. Subsequently, the integration of PHA synthesis genes in NHL18 resulting in strain SM23 allowed the cell to accumulate 15 % cell dry weight of PHO with a final titer of 1.54 ± 0.234 g/L from glycerol in fed-batch fermentation.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 232-240"},"PeriodicalIF":6.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895573","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":"Lipid accumulation in nitrogen and phosphorus-limited yeast is caused by less growth-related dilution","authors":"Xi Li ,&nbsp;Daniel R. Weilandt ,&nbsp;Felix C. Keber ,&nbsp;Arjuna M. Subramanian ,&nbsp;Shayne R. Loynes ,&nbsp;Christopher V. Rao ,&nbsp;Yihui Shen ,&nbsp;Martin Wühr ,&nbsp;Joshua D. Rabinowitz","doi":"10.1016/j.ymben.2025.08.010","DOIUrl":"10.1016/j.ymben.2025.08.010","url":null,"abstract":"<div><div>Oleaginous yeasts are used commercially to produce oleochemicals and hold potential also for biodiesel production. In response to nitrogen or phosphorous limitation, oleaginous yeasts accumulate lipids in the form of triacylglycerols. Previous work has investigated potential mechanisms by which nutrient limitation induces lipid biosynthesis without verifying whether lipid biosynthesis flux is actually enhanced. Here we show, using ¹³C-glucose tracing, that in nitrogen or phosphorous limitation, lipid accumulation occurs without consistent increases in biosynthetic flux. Instead, the main driver of increased lipid pools is decreased growth-related dilution. This conclusion holds across two divergent oleaginous yeasts: <em>Rhodotorula toruloides</em> and <em>Yarrowia lipolytica</em>. Quantitative proteomics shows a substantial proteome reallocation in response to nitrogen and phosphorous limitation, with ribosomal proteins strongly downregulated, while lipid enzymes are preserved but not consistently upregulated in absolute quantity. Thus, nutrient limitation, rather than triggering greatly enhanced lipid synthesis, results in roughly sustained lipid enzyme levels and biosynthetic flux. Due to slower lipid dilution by cell division, this suffices to drive marked lipid accumulation.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"93 ","pages":"Pages 60-72"},"PeriodicalIF":6.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900577","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":"Pan-reactome analysis of Streptomyces strains reveals association and disconnection between primary and secondary metabolism","authors":"Byung Tae Lee ,&nbsp;Omkar S. Mohite ,&nbsp;Mun Su Kwon ,&nbsp;Hahk-Soo Kang ,&nbsp;Tilmann Weber ,&nbsp;Sang Yup Lee ,&nbsp;Hyun Uk Kim","doi":"10.1016/j.ymben.2025.08.005","DOIUrl":"10.1016/j.ymben.2025.08.005","url":null,"abstract":"<div><div>Secondary metabolites have crucial medicinal and industrial applications, but their alignment with primary metabolism remains unclear. As secondary metabolism depends on primary metabolism for precursor supply, we present a pan-reactome analysis of 242 <em>Streptomyces</em> strains to investigate their association and disconnection. This analysis includes phylogenetic grouping of the strains using genome data, and uniform manifold approximation and projection (UMAP) analysis of their genome-scale metabolic models (GEMs) and biosynthetic gene cluster (BGC) data, which represent biochemical reactions in primary and secondary metabolism. Subsequent correlation analysis of the preprocessed GEM and BGC data showed a Pearson correlation coefficient of 0.54, revealing both metabolic association and disconnection. In particular, among 47 precursors of polyketides, nonribosomal peptides, and hybrids, nine precursors required by these BGCs were predicted to be non-producible due to missing genes in primary metabolism or BGCs. The pan-reactome analysis facilitates the identification of precursor availability and metabolic gaps, providing insights into secondary metabolite biosynthesis.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 241-251"},"PeriodicalIF":6.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895574","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":"Advances in metabolic engineering of Vibrio natriegens as an unconventional host for biotechnology","authors":"Maurice Hädrich ,&nbsp;Josef Hoff ,&nbsp;Bastian Blombach","doi":"10.1016/j.ymben.2025.08.008","DOIUrl":"10.1016/j.ymben.2025.08.008","url":null,"abstract":"<div><div>The exploitation of <em>Vibrio natriegens</em> as an unconventional host for biotechnology has progressed rapidly. This development is not only a result of the remarkable high growth rate of this marine bacterium on different substrates but is also possible due to good handling properties, a versatile metabolism and its inherent natural competence – features that have facilitated the development of a sophisticated genetic engineering and synthetic biology toolbox. The availability of robust metabolic and regulatory data enables a model-based quantitative description of metabolic routes and accelerates rational metabolic engineering of the facultative anaerobic bacterium. As reviewed here, numerous examples, ranging from small-molecule production over cell-free protein synthesis to bioremediation render <em>V. natriegens</em> a promising next-generation host for biotechnological applications.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 217-231"},"PeriodicalIF":6.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892258","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 genome-scale CRISPR deletion screen in Chinese hamster ovary cells reveals essential regions of the coding and non-coding genome","authors":"Federico De Marco ,&nbsp;Ivy Rose Sebastian ,&nbsp;Antonino Napoleone ,&nbsp;Alexander Molin ,&nbsp;Markus Riedl ,&nbsp;Nina Bydlinski ,&nbsp;Krishna Motheramgari ,&nbsp;Mohamed K. Hussein ,&nbsp;Lovro Kramer ,&nbsp;Thomas Kelly ,&nbsp;Thomas Jostock ,&nbsp;Nicole Borth","doi":"10.1016/j.ymben.2025.08.007","DOIUrl":"10.1016/j.ymben.2025.08.007","url":null,"abstract":"<div><div>The biopharmaceutical sector relies on CHO cells to investigate biological processes and as the preferred host for production of biotherapeutics. Simultaneously, advancements in CHO cell genome assembly have provided insights for developing sophisticated genetic engineering strategies. While the majority of these efforts have focused on coding genes, with some interest in transcribed non-coding RNAs (e.g., microRNAs and lncRNAs), there remains a lack of genome-wide systematic studies that precisely examine the remaining 90 % of the genome and its impact on cellular phenotypes. This unannotated “dark matter” includes regulatory elements and other poorly characterized genomic features that may be potentially critical for cell behaviour. In this study, we deployed a genome-scale CRISPR screening platform with 112,272 paired guide RNAs targeting 14,034 genomic regions for complete deletion of 150 kb long sections. This platform enabled the execution of a negative screen that selectively identified dying cells to determine regions essential for cell survival. By using paired gRNAs, we overcame the intrinsic limitations of traditional frameshift strategies, which will likely have little or no effect on the non-coding genome. This study revealed 427 regions essential for CHO cell survival, many of which currently lack gene annotation or known functions. For these regions, we present their annotation status, transcriptional activity and annotated chromatin states. Selected regions, particularly those lacking all of the above, were individually deleted to confirm their essentiality. This work sheds a novel light on a substantial portion of the mammalian genome that has been traditionally difficult to investigate and therefore neglected. Notably, the fact that the deletion of some of these regions is lethal to cells suggests they encode critical regulatory functions. A better genome-wide understanding of these functions could open new avenues for engineering cells with improved bioprocess relevant properties.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 194-207"},"PeriodicalIF":6.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885422","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":"Retrofitting Escherichia coli for de novo production of rare L-sorbose from abundant D-glucose","authors":"Jayce E. Taylor ,&nbsp;Trevor Gannalo ,&nbsp;Bryant Luu ,&nbsp;Dileep Sai Kumar Palur ,&nbsp;Augustine Arredondo ,&nbsp;Ian C. Anderson ,&nbsp;Twisha Dasgupta ,&nbsp;John Didzbalis ,&nbsp;Justin B. Siegel ,&nbsp;Shota Atsumi","doi":"10.1016/j.ymben.2025.08.006","DOIUrl":"10.1016/j.ymben.2025.08.006","url":null,"abstract":"<div><div>Monosaccharides exist in either “D” or “L” conformations, with L-sugars being much less abundant in nature and therefore classified as “rare sugars.” Rare sugars hold significant potential due to their unique interactions with biological systems, offering health, food, and crop benefits. One such sugar, L-sorbose, serves as a critical precursor to Vitamin C and offers a low-calorie, moderately sweet alternative to table sugar, being 60–70 % as sweet but with only 25 % of the caloric value. However, the broader study and application of rare sugars, including L-sorbose, are constrained by their high cost and limited availability. To address this challenge, we developed a biosynthetic strategy to convert the abundant and inexpensive D-sugar D-glucose into the rare L-sugar L-sorbose using microbial production. By utilizing phosphorylation and dephosphorylation steps to thermodynamically drive carbon flux, efficient production of 14.5 g L⁻¹ L-sorbose was achieved under test tube conditions. Additionally, this pathway results in the co-production of D-sedoheptulose, a non-sweet, rare sugar shown to inhibit C6 sugar consumption in humans by modulating energy metabolism. The dual production of L-sorbose and D-sedoheptulose presents unique opportunities for applications in food and health sciences. This study demonstrates microbial production as a promising platform for rare L-sugar biosynthesis and provides a generalizable strategy for converting abundant D-sugars into underexplored L-sugars. Expanding access to L-sugars enables deeper investigations into their biological functions, metabolic pathways, and industrial applications. By advancing both fundamental sugar metabolism research and microbial production strategies, this study broadens the scope of rare sugar utilization.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"92 ","pages":"Pages 208-216"},"PeriodicalIF":6.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873966","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}