Metabolic engineering最新文献

{"title":"Engineering the cellulolytic bacterium, Clostridium thermocellum, to co-utilize hemicellulose","authors":"Katherine J. Chou ,&nbsp;Trevor Croft ,&nbsp;Skyler D. Hebdon ,&nbsp;Lauren R. Magnusson ,&nbsp;Wei Xiong ,&nbsp;Luis H. Reyes ,&nbsp;Xiaowen Chen ,&nbsp;Emily J. Miller ,&nbsp;Danielle M. Riley ,&nbsp;Sunnyjoy Dupuis ,&nbsp;Kathrin A. Laramore ,&nbsp;Lisa M. Keller ,&nbsp;Dirk Winkelman ,&nbsp;Pin-Ching Maness","doi":"10.1016/j.ymben.2024.03.008","DOIUrl":"10.1016/j.ymben.2024.03.008","url":null,"abstract":"<div><p>Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and <em>Clostridium thermocellum</em> is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by <em>C. thermocellum</em> is approached with co-cultures, because <em>C. thermocellum</em> does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered <em>C. thermocellum</em> to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different β-xylosidase enzymes originating from <em>Thermoanaerobacterium saccharolyticum</em> into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the β-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported <em>C. thermocellum</em> strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 193-205"},"PeriodicalIF":8.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786785","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":"Efficient production of (S)-limonene and geraniol in Saccharomyces cerevisiae through the utilization of an Erg20 mutant with enhanced GPP accumulation capability","authors":"Armand Bernard ,&nbsp;Seungwoo Cha ,&nbsp;Hyesoo Shin ,&nbsp;Daeyeol Lee ,&nbsp;Ji-Sook Hahn","doi":"10.1016/j.ymben.2024.04.003","DOIUrl":"https://doi.org/10.1016/j.ymben.2024.04.003","url":null,"abstract":"<div><p>Monoterpenes and monoterpenoids such as (<em>S</em>)-limonene and geraniol are valuable chemicals with a wide range of applications, including cosmetics, pharmaceuticals, and biofuels. <em>Saccharomyces cerevisiae</em> has proven to be an effective host to produce various terpenes and terpenoids. (<em>S</em>)-limonene and geraniol are produced from geranyl pyrophosphate (GPP) through the enzymatic actions of limonene synthase (LS) and geraniol synthase (GES), respectively. However, a major hurdle in their production arises from the dual functionality of the Erg20, a farnesyl pyrophosphate (FPP) synthase, responsible for generating GPP. Erg20 not only synthesizes GPP by condensing isopentenyl pyrophosphate (IPP) with dimethylallyl pyrophosphate but also catalyzes further condensation of IPP with GPP to produce FPP. In this study, we have tackled this issue by harnessing previously developed Erg20 mutants, Erg20^K197G (Erg20^G) and Erg20^{F96W, N127W} (Erg20^WW), which enhance GPP accumulation. Through a combination of these mutants, we generated a novel Erg20^WWG mutant with over four times higher GPP accumulating capability than Erg20^WW, as observed through geraniol production levels. The Erg20^WWG mutant was fused to the LS from <em>Mentha spicata</em> or the GES from <em>Catharanthus roseus</em> for efficient conversion of GPP to (<em>S</em>)-limonene and geraniol, respectively. Further improvements were achieved by localizing the entire mevalonate pathway and the Erg20^WWG-fused enzymes in peroxisomes, while simultaneously downregulating the essential <em>ERG20</em> gene using the glucose-sensing <em>HXT1</em> promoter. In the case of (<em>S</em>)-limonene production, additional Erg20^WWG-LS was expressed in the cytosol. As a result, the final strains produced 1063 mg/L of (<em>S</em>)-limonene and 1234 mg/L of geraniol by fed-batch biphasic fermentations with ethanol feeding. The newly identified Erg20^WWG mutant opens doors for the efficient production of various other GPP-derived chemicals including monoterpene derivatives and cannabinoids.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 183-192"},"PeriodicalIF":8.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140649963","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":"Combinatorial metabolic engineering of Bacillus subtilis for de novo production of polymyxin B","authors":"Hui-Zhong Sun ,&nbsp;Qing Li ,&nbsp;Wei Shang ,&nbsp;Bin Qiao ,&nbsp;Qiu-Man Xu ,&nbsp;Jing-Sheng Cheng","doi":"10.1016/j.ymben.2024.04.001","DOIUrl":"10.1016/j.ymben.2024.04.001","url":null,"abstract":"<div><p>Polymyxin is a lipopeptide antibiotic that is effective against multidrug-resistant Gram-negative bacteria. However, its clinical development is limited due to low titer and the presence of homologs. To address this, the polymyxin gene cluster was integrated into <em>Bacillus subtilis</em>, and <em>sfp</em> from <em>Paenibacillus polymyxa</em> was expressed heterologously, enabling recombinant <em>B. subtilis</em> to synthesize polymyxin B. Regulating NRPS domain inhibited formation of polymyxin B2 and B3. The production of polymyxin B increased to 329.7 mg/L by replacing the native promoters of <em>pmxA</em>, <em>pmxB</em>, and <em>pmxE</em> with P<em>fusA</em>, C2up, and P<em>fusA</em>, respectively. Further enhancement in this production, up to 616.1 mg/L, was achieved by improving the synthesis ability of 6-methyloctanoic acid compared to the original strain expressing polymyxin heterologously. Additionally, incorporating an anikasin-derived domain into the hybrid nonribosomal peptide synthase of polymyxin increased the B1 ratio in polymyxin B from 57.5% to 62.2%. Through optimization of peptone supply in the fermentation medium and fermentation in a 5.0-L bioreactor, the final polymyxin B titer reached 962.1 mg/L, with a yield of 19.24 mg/g maltodextrin and a productivity of 10.02 mg/(L·h). This study demonstrates a successful approach for enhancing polymyxin B production and increasing the B1 ratio through combinatorial metabolic engineering.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 123-136"},"PeriodicalIF":8.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140534661","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":"Rethinking 13C-metabolic flux analysis – The Bayesian way of flux inference","authors":"Axel Theorell ,&nbsp;Johann F. Jadebeck ,&nbsp;Wolfgang Wiechert ,&nbsp;Johnjoe McFadden ,&nbsp;Katharina Nöh","doi":"10.1016/j.ymben.2024.03.005","DOIUrl":"https://doi.org/10.1016/j.ymben.2024.03.005","url":null,"abstract":"<div><p>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 (¹³C-MFA), which uses a dataset-model combination to determine the fluxes. Bayesian statistical methods are gaining popularity in the field of life sciences, but the use of ¹³C-MFA is still dominated by conventional best-fit approaches. The slow take-up of Bayesian approaches is, at least partly, due to the unfamiliarity of Bayesian methods to metabolic engineering researchers. To address this unfamiliarity, we here outline similarities and differences between the two approaches and highlight particular advantages of the Bayesian way of flux analysis. With a real-life example, re-analysing a moderately informative labelling dataset of <em>E. coli,</em> we identify situations in which Bayesian methods are advantageous and more informative, pointing to potential pitfalls of current ¹³C-MFA evaluation approaches. We propose the use of Bayesian model averaging (BMA) for flux inference as a means of overcoming the problem of model uncertainty through its tendency to assign low probabilities to both, models that are unsupported by data, and models that are overly complex. In this capacity, BMA resembles a tempered Ockham's razor. With the tempered razor as a guide, BMA-based ¹³C-MFA alleviates the problem of model selection uncertainty and is thereby capable of becoming a game changer for metabolic engineering by uncovering new insights and inspiring novel approaches.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 137-149"},"PeriodicalIF":8.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559145","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":"Nature as blueprint: Global phenotype engineering of CHO production cells based on a multi-omics comparison with plasma cells","authors":"Nadja Raab ,&nbsp;Nikolas Zeh ,&nbsp;Robin Kretz ,&nbsp;Linus Weiß ,&nbsp;Anna Stadermann ,&nbsp;Benjamin Lindner ,&nbsp;Simon Fischer ,&nbsp;Dieter Stoll ,&nbsp;Kerstin Otte","doi":"10.1016/j.ymben.2024.03.007","DOIUrl":"10.1016/j.ymben.2024.03.007","url":null,"abstract":"<div><p>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 in mammals, we performed a comprehensive multi-omics comparison between CHO and plasma cells to exploit optimized cellular production traits. Comparing the transcriptome, proteome, miRNome, surfaceome and secretome of both cell lines identified key differences including 392 potential overexpression targets for CHO cell engineering categorized in 15 functional classes like transcription factors, protein processing or secretory pathway. In addition, 3 protein classes including 209 potential knock-down/out targets for CHO engineering were determined likely to affect aggregation or proteolysis. For production phenotype engineering, several of these novel targets were successfully applied to transient and transposase mediated overexpression or knock-down strategies to efficiently improve productivity of CHO cells. Thus, substantial improvement of CHO productivity was achieved by taking nature as a blueprint for cell line engineering.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 110-122"},"PeriodicalIF":8.4,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336212","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":"Resource allocation modeling for autonomous prediction of plant cell phenotypes","authors":"Anne Goelzer ,&nbsp;Loïc Rajjou ,&nbsp;Fabien Chardon ,&nbsp;Olivier Loudet ,&nbsp;Vincent Fromion","doi":"10.1016/j.ymben.2024.03.009","DOIUrl":"10.1016/j.ymben.2024.03.009","url":null,"abstract":"<div><p>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 <em>Arabidopsis thaliana</em>, 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 plant cell growth and survival and localized in cellular compartments. We simulated the model for varying environmental conditions of temperature, irradiance, partial pressure of CO₂ and O₂, and compared RBA predictions to known resource distributions and quantitative phenotypic traits such as the relative growth rate, the C:N ratio, and finally to the empirical characteristics of CO₂ fixation given by the well-established Farquhar model. In comparison to other standard constraint-based modeling methods like Flux Balance Analysis, the RBA model makes accurate quantitative predictions without the need for empirical constraints. Altogether, we show that RBA significantly improves the autonomous prediction of plant cell phenotypes in complex environmental conditions, and provides mechanistic links between the genotype and the phenotype of the plant cell.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 86-101"},"PeriodicalIF":8.4,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336213","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":"Repurposing plant hormone receptors as chemically-inducible genetic switches for dynamic regulation in yeast","authors":"Shuang Wei ,&nbsp;Mengwan Li ,&nbsp;Xuye Lang ,&nbsp;Nicholas R. Robertson ,&nbsp;Sang-Youl Park ,&nbsp;Sean R. Cutler ,&nbsp;Ian Wheeldon","doi":"10.1016/j.ymben.2024.03.006","DOIUrl":"10.1016/j.ymben.2024.03.006","url":null,"abstract":"<div><p>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 system for the multi-stress tolerant yeast <em>Kluyveromyces marxianus</em> and use it to tune ethyl acetate production, a native metabolite produced at high titers in this yeast. To achieve this, we repurposed the plant hormone sensing modules (PYR1^ABA/HAB1 and PYR1*^MANDI/HAB1*) for high dynamic-range gene activation and repression controlled by either abscisic acid (ABA) or mandipropamid (mandi). To redirect metabolic flux towards ethyl acetate biosynthesis, we simultaneously repress pyruvate dehydrogenase (<em>PDA1</em>) and activate pyruvate decarboxylase (<em>PDC1</em>) to enhance ethyl acetate titers. Thus, we have developed new tools for chemically tuning gene expression in <em>K. marxianus</em> and <em>S. cerevisiae</em> that should be deployable across many non-conventional eukaryotic hosts.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 102-109"},"PeriodicalIF":8.4,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S109671762400051X/pdfft?md5=d0e3ee6773439cd9f4e30d05abde4f72&pid=1-s2.0-S109671762400051X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing the E. coli platform for efficient production of UMP-derived chemicals","authors":"Le Yu ,&nbsp;Yaojie Gao ,&nbsp;Yuanyuan He ,&nbsp;Yang Liu ,&nbsp;Jianning Shen ,&nbsp;Han Liang ,&nbsp;Rong Gong ,&nbsp;He Duan ,&nbsp;Neil P.J. Price ,&nbsp;Xuemin Song ,&nbsp;Zixin Deng ,&nbsp;Wenqing Chen","doi":"10.1016/j.ymben.2024.03.004","DOIUrl":"10.1016/j.ymben.2024.03.004","url":null,"abstract":"<div><p>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 <em>E. coli,</em> for the first time, <em>via</em> a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the <em>E. coli</em> cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in <em>E. coli</em> MB229 (a <em>ΔthyA</em> strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered <em>E. coli</em> for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of <em>E. coli</em> as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 61-74"},"PeriodicalIF":8.4,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207265","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 of Escherichia coli for high-level production of the biodegradable polyester monomer 2-pyrone-4,6-dicarboxylic acid","authors":"Fengli Wu ,&nbsp;Shucai Wang ,&nbsp;Dan Zhou ,&nbsp;Shukai Gao ,&nbsp;Guotian Song ,&nbsp;Yanxia Liang ,&nbsp;Qinhong Wang","doi":"10.1016/j.ymben.2024.03.003","DOIUrl":"10.1016/j.ymben.2024.03.003","url":null,"abstract":"<div><p>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 overproducing strain. Consequently, the one-step biosynthesis of PDC from glucose was achieved. Further, the PDC production was enhanced by multi-copy integration of the key gene <em>PsligC</em> encoding 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase and co-expression of <em>Vitreoscilla</em> hemoglobin. Subsequently, the PDC production was substantially improved by redistributing the metabolic flux for cell growth and PDC biosynthesis based on dynamically downregulating the expression of pyruvate kinase. The resultant strain PDC50 produced 129.37 g/L PDC from glucose within 78 h under fed-batch fermentation conditions, with a yield of 0.528 mol/mol and an average productivity of 1.65 g/L/h. The findings of this study lay the foundation for the potential industrial production of PDC.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 52-60"},"PeriodicalIF":8.4,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194161","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":"Parageobacillus thermoglucosidasius as an emerging thermophilic cell factory","authors":"Miguel Paredes-Barrada ,&nbsp;Panagiotis Kopsiaftis ,&nbsp;Nico J. Claassens ,&nbsp;Richard van Kranenburg","doi":"10.1016/j.ymben.2024.03.001","DOIUrl":"10.1016/j.ymben.2024.03.001","url":null,"abstract":"<div><p><em>Parageobacillus thermoglucosidasius</em> 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 degradation and fermentation to occur at the same temperature in a Simultaneous Saccharification and Fermentation (SSF) or Consolidated Bioprocessing (CBP) approach. Its natural hemicellulolytic capabilities and its ability to convert CO to metabolic energy make <em>P</em>. <em>thermoglucosidasius</em> a potentially attractive host for bio-based processes. It can effectively degrade hemicellulose due to a number of hydrolytic enzymes, carbohydrate transporters, and regulatory elements coded from a genomic cluster named Hemicellulose Utilization (HUS) locus. The growing availability of effective genetic engineering tools in <em>P. thermoglucosidasius</em> further starts to open up its potential as a versatile thermophilic cell factory. A number of strain engineering examples showcasing the potential of <em>P. thermoglucosidasius</em> as a microbial chassis for the production of bulk and fine chemicals are presented along with current research bottlenecks. Ultimately, this review provides a holistic overview of the distinct metabolic characteristics of <em>P. thermoglucosidasius</em> and discusses research focused on expanding the native metabolic boundaries for the development of industrially relevant strains.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"83 ","pages":"Pages 39-51"},"PeriodicalIF":8.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1096717624000363/pdfft?md5=48bcdb657e9058a88cf42fddd59d9f19&pid=1-s2.0-S1096717624000363-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}