Metabolic engineering最新文献

{"title":"Computer-assisted multilevel optimization of malonyl-CoA availability in Pseudomonas putida","authors":"Christos Batianis ,&nbsp;Rik P. van Rosmalen ,&nbsp;Pedro Moñino Fernández ,&nbsp;Konstantinos Labanaris ,&nbsp;Enrique Asin-Garcia ,&nbsp;Maria Martin-Pascual ,&nbsp;Markus Jeschek ,&nbsp;Ruud A. Weusthuis ,&nbsp;Maria Suarez-Diez ,&nbsp;Vitor A.P. Martins dos Santos","doi":"10.1016/j.ymben.2025.03.008","DOIUrl":"10.1016/j.ymben.2025.03.008","url":null,"abstract":"<div><div>Malonyl-CoA is the major precursor for the biosynthesis of diverse industrially valuable products such as fatty acids/alcohols, flavonoids, and polyketides. However, its intracellular availability is limited in most microbial hosts, hampering the industrial production of such chemicals. To address this limitation, we present a multilevel optimization workflow using modern metabolic engineering technologies to systematically increase the malonyl-CoA levels in <em>Pseudomonas putida</em>. The workflow involves the identification of gene downregulations, chassis selection, and optimization of the acetyl-CoA carboxylase complex through ribosome binding site engineering. Computational tools and high-throughput screening with a malonyl-CoA biosensor enabled the rapid evaluation of numerous genetic targets. Combining the most beneficial targets led to a 5.8-fold enhancement in the production titer of the valuable polyketide phloroglucinol. This study demonstrates the effective integration of computational and genetic technologies for engineering <em>P. putida</em>, opening new avenues for the development of industrially relevant strains and the investigation of fundamental biological questions.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 165-177"},"PeriodicalIF":6.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664001","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":"Stress-driven dynamic regulation of multiple genes to reduce accumulation of toxic aldehydes","authors":"Shan Yuan ,&nbsp;Chao Xu ,&nbsp;Miaomiao Jin ,&nbsp;Xinglin Jiang ,&nbsp;Wei Liu ,&nbsp;Mo Xian ,&nbsp;Ping Jin","doi":"10.1016/j.ymben.2025.03.009","DOIUrl":"10.1016/j.ymben.2025.03.009","url":null,"abstract":"<div><div>Aldehydes are ubiquitous metabolites in living cells. As reactive electrophiles, they have the capacity to form adducts with cellular protein thiols and amines, leading to potential toxicity. Dynamic regulation has proven to be an effective strategy for addressing the accumulation of toxic metabolites. However, there are limited reports on applying dynamic control specifically to mitigate aldehyde accumulation. In this study, the cinnamaldehyde accumulation in the biosynthesis of cinnamylamine was used as a model to evaluate a two-way dynamic regulation strategy. First, we utilized whole-genome transcript arrays to identify the cinnamaldehyde-responsive promoters: the upregulated promoter P₄ and the downregulated promoter P_d. They were then employed as biosensors to dynamically regulate the synthesis and consumption of cinnamaldehyde, mitigating its toxic effects on the host. This strategy successfully reduced cinnamaldehyde accumulation by 50 % and increased the production of cinnamylamine by 2.9 times. This study demonstrated a cinnamaldehyde-induced autoregulatory system that facilitated the conversion of cinnamic acid into cinnamylamine without the need for costly external inducers, presenting a promising and economically viable approach. The strategy also serves as a reference for alleviating the inhibitory effects of other toxic aldehydes on microorganisms. Additionally, the biosensors (P_d and P₄) can respond to a range of aldehyde compounds, offering a rapid and sensitive method for detecting toxic aldehydes in both environmental samples and microorganisms, thus provide a valuable tool for screening strains enhanced aldehyde yield.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 129-140"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630610","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":"Scaling metabolic model reconstruction up to the pan-genome level: A systematic review and prospective applications to photosynthetic organisms","authors":"Marius Arend ,&nbsp;Emilian Paulitz ,&nbsp;Yunli Eric Hsieh ,&nbsp;Zoran Nikoloski","doi":"10.1016/j.ymben.2025.02.015","DOIUrl":"10.1016/j.ymben.2025.02.015","url":null,"abstract":"<div><div>Advances in genomics technologies have generated large data sets that provide tremendous insights into the genetic diversity of taxonomic groups. However, it remains challenging to pinpoint the effect of genetic diversity on different traits without performing resource-intensive phenotyping experiments. Pan-genome-scale metabolic models (panGEMs) extend traditional genome-scale metabolic models by considering the entire reaction repertoire that enables the prediction and comparison of metabolic capabilities within a taxonomic group. Here, we systematically review the state-of-the-art methodologies for constructing panGEMs, focusing on used tools, databases, experimental datasets, and orthology relationships. We highlight the unique advantages of panGEMs compared to single-species GEMs in predicting metabolic phenotypes and in guiding the experimental validation of genome annotations. In addition, we emphasize the disparity between the available (pan-)genomic data on photosynthetic organisms and their under-representation in current (pan)GEMs. Finally, we propose a perspective for tackling the reconstruction of panGEMs for photosynthetic eukaryotes that can help advance our understanding of the metabolic diversity in this taxonomic group.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 67-77"},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620240","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 Halomonas bluephagenesis for pilot production of terpolymers containing 3-hydroxybutyrate, 4-hydroxybutyrate and 3-hydroxyvalerate from glucose","authors":"Hongtao He ,&nbsp;Ng Wuh Jer ,&nbsp;Qitiao Hu ,&nbsp;Zhongnan Zhang ,&nbsp;Simian Sun ,&nbsp;Geyuan Xu ,&nbsp;Shimao Yang ,&nbsp;Shuang Zheng ,&nbsp;Fuqing Wu ,&nbsp;Qiong Wu ,&nbsp;Guo-Qiang Chen","doi":"10.1016/j.ymben.2025.03.003","DOIUrl":"10.1016/j.ymben.2025.03.003","url":null,"abstract":"<div><div>Microbial poly(3-hydroxybutyrate-<em>co-</em>4-hydroxybutyrate-<em>co-</em>3-hydroxyvalerate), abbreviated as P(3HB-4HB-3HV) or P34HBHV, is a flexible polyhydroxyalkanoate (PHA) material ranging from softness to elasticity depending on the ratios of various monomers. <em>Halomonas bluephagenesis</em>, as the chassis of the next generation industrial biotechnology (NGIB) able to grow contamination free under open unsterile conditions. The resulting recombinants of <em>H. bluephagenesis</em> became capable of efficiently synthesizing P34HBHV utilizing glucose as the sole carbon source. Engineered <em>H. bluephagenesis</em> H1 (encoding <em>ogdA, sucD, 4hbD, orfZ, scpA</em> and <em>scpB</em> in chromosomes) transformed with a plasmid containing PHA synthesis genes <em>phaC</em> and <em>phaA</em> and its derivative H29 produced up to 92 % P(3HB-<em>co</em>-8.85 %4HB-<em>co</em>-8.47 %3HV) and 72 % P(3HB-<em>co</em>-13.21 %4HB-<em>co</em>-11.97 %3HV) in cell dry weight (CDW), respectively, in shake flasks. In bioreactor cultivation, <em>H. bluephagenesis</em> H39 constructed by integrating the <em>4hbD</em>, <em>phaC</em> and <em>phaA</em> genes into the genome of <em>H. bluephagenesis</em> H1 achieved 95 g/L CDW with 69 % P(3HB-<em>co</em>-10.49 %4HB-<em>co</em>-3.54 %3HV), while <em>H. bluephagenesis</em> H43, further optimized with <em>lpxM</em> deletion, reached 73 g/L CDW with 78 % P(3HB-<em>co</em>-10.35 %4HB-<em>co</em>-4.54 %3HV) in a 100 L bioreactor. For the first time, <em>H. bluephagenesis</em> was successfully engineered to generate stable and hyperproductive derivative strains for pilot production of P(3HB-4HB-3HV) with customizable monomer ratios from glucose as the sole carbon source.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 117-128"},"PeriodicalIF":6.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625391","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":"Mechanism and engineering of endoplasmic reticulum-localized membrane protein folding in Saccharomyces cerevisiae","authors":"Yuhuan Luo,&nbsp;Jian-Jiang Zhong,&nbsp;Han Xiao","doi":"10.1016/j.ymben.2025.03.006","DOIUrl":"10.1016/j.ymben.2025.03.006","url":null,"abstract":"<div><div>Correct folding of endoplasmic reticulum (ER)-localized membrane proteins, such as cytochrome P450, endows a synthetic biology host with crucial catalytic functions, which is of vital importance in the field of metabolic engineering and synthetic biology. However, due to complexed interaction with cellular membrane environment and other proteins (e.g., molecular chaperone) regulation, a substantial proportion of heterologous membrane proteins cannot be properly folded in the ER of <em>Saccharomyces cerevisiae</em>, a widely used synthetic biology host. In this review, we first introduce the four steps in membrane protein folding process and the affecting factors including the amino acid sequence of membrane protein, the folding process, molecular chaperones, quality control mechanism, and lipid environment in <em>S. cerevisiae.</em> Then, we summarize the metabolic engineering strategies to enhance the correct folding of ER-localized membrane proteins, such as by engineering and <em>de novel</em> design of membrane protein, regulation of the co-translational folding process, co-expression of molecular chaperones, modulation of ER quality, and lipids engineering. Finally, we discuss the limitations of current strategies and propose future research directions to address the key issues.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 43-56"},"PeriodicalIF":6.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597319","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":"Bioconversion of CO2 into valuable bioproducts via synthetic modular co-culture of engineered Chlamydomonas reinhardtii and Escherichia coli","authors":"Nam Kyu Kang ,&nbsp;Hyun Gi Koh ,&nbsp;Yujung Choi ,&nbsp;Hyunjun Min ,&nbsp;Donald R. Ort ,&nbsp;Yong-Su Jin","doi":"10.1016/j.ymben.2025.03.004","DOIUrl":"10.1016/j.ymben.2025.03.004","url":null,"abstract":"<div><div>With increasing concern over environmental problems and energy crises, interest in the biological conversion of CO₂ into bioproducts is growing. Although microalgae efficiently utilize CO₂, their metabolic engineering remains challenging. In contrast, while synthetic biology tools are advanced for many heterotrophic bacteria, these organisms cannot directly utilize CO₂. As such, a modular co-culture system with a glycolate dehydrogenase 1 (GYD1) deficient C<em>hlamydomonas reinhardtii</em> mutant and <em>Escherichia coli</em> was developed. The GYD1 mutant secretes glycolic acid via photorespiration, which <em>E. coli</em> metabolizes via the glyoxylate cycle. <em>E. coli</em> growth was improved by implementing two-stage continuous systems to 2.0 mg L⁻¹ h⁻¹ on CO₂. The production of green fluorescent protein (0.52 ng L⁻¹ h⁻¹) and lycopene (6.3 μg L⁻¹ h⁻¹) was also demonstrated. This study represents a successful case of a synthetic modular co-culture with a microalga and a heterotrophic bacterium, potentially contributing to sustainable industrial processes and reducing environmental impact.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 57-66"},"PeriodicalIF":6.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586283","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":"Exploring the versatility of fatty acid biosynthesis in Escherichia coli: Production of random methyl branched fatty acids","authors":"Fernando Bracalente ,&nbsp;Matías Tripaldi ,&nbsp;Virginia Galván ,&nbsp;Yi-Ting Tsai ,&nbsp;Eriko Takano ,&nbsp;Silvia Altabe ,&nbsp;Hugo Gramajo ,&nbsp;Ana Arabolaza","doi":"10.1016/j.ymben.2025.03.005","DOIUrl":"10.1016/j.ymben.2025.03.005","url":null,"abstract":"<div><div>Microbial fatty acids (FAs) hold significant potential as alternatives for the oleochemical industry. However, expanding the functional and structural diversity of microbial FA-derived products is essential to fully leverage this potential. Methyl-branched-chain FAs (MBFAs) are of particular interest as high-performance industrial compounds. This study examines the ability of the <em>Escherichia coli</em> FA biosynthesis pathway to produce a diverse mixture of random MBFAs (R-MBFAs) by utilizing both the natural malonyl-ACP substrate and the branched-chain methylmalonyl-ACP (mm-ACP) as an unnatural elongation unit. First, <em>E. coli</em> was engineered to accumulate methylmalonyl-CoA (mm-CoA) through a methylmalonate or a propionate-dependent pathway, and the capacity of <em>E. coli</em> FASII enzymes to synthesize mm-ACP and utilize it as a substrate was confirmed by the production of R-MBFAs. However, low R-MBFA accumulation and propionate-induced growth inhibition was observed. To improve R-MBFA yields, various malonyl-/mm-CoA acyltransferase (AT) enzymes were expressed, and their efficacy in generating mm-ACP was indirectly assessed through R-MBFA production levels. When expressing selected ATs, including native malonyl CoA-acyl carrier protein transacylase FabD, propionate-induced growth inhibition was alleviated and R-MBFA titers ranged from 5.9% to 7.7% of total FAs. Further strain optimization, analyzing two thioesterase (TE) activities and overexpression of the <em>E. coli</em> transciptional regulator ^<em>Ec</em>FadR, significantly boosted R-MBFA titers. While an engineered strain carrying the <em>Mus musculus</em> TE domain (^<em>Mm</em>TE) produced 55.2 mg/L of R-MBFAs, representing an 11.8% of total FAs, another strain combining the overexpression of the cytosolic version of the TE TesA from <em>E. coli</em> (^<em>Ec</em>‘TesA) and ^<em>Ec</em>FadR produced approximately 1.1 g/L of total FAs, with an R-MBFA fraction of 6.7% (70.5 mg/L), marking the highest yield recorded in shake-flask cultures. Finally, these two recombinant <em>E. coli</em> strains were grown in laboratory-scale fed-batch fermentations, and produced approximately 10 g/L of total FAs and over 1–1.2 g/L of R-MBFAs, underscoring the potential for large-scale production of these valuable FA-derived compounds.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 78-91"},"PeriodicalIF":6.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586285","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":"Hybrid biological-chemical strategy for converting polyethylene into a recyclable plastic monomer using engineered Corynebacterium glutamicum","authors":"Chunjun Zhan ,&nbsp;Guangxu Lan ,&nbsp;Qingyun Dan ,&nbsp;Ning Qin ,&nbsp;Allie Pearson ,&nbsp;Peter Mellinger ,&nbsp;Yuzhong Liu ,&nbsp;Zilong Wang ,&nbsp;Seokjung Cheong ,&nbsp;Chang Dou ,&nbsp;Chenyi Li ,&nbsp;Robert Haushalter ,&nbsp;Jay D. Keasling","doi":"10.1016/j.ymben.2025.03.007","DOIUrl":"10.1016/j.ymben.2025.03.007","url":null,"abstract":"<div><div>Converting polyethylene (PE) into valuable materials, particularly ones that are better for the environment than the incumbent plastics, not only helps mitigate environmental issues caused by plastic waste but also alleviates the long-standing problem of microbial fermentation competing with food supplies. However, the inherent robustness of PE due to its strong carbon-carbon bonds and high molecular weight necessitates harsh decomposition conditions, resulting in diverse decomposition outcomes that present significant challenges for downstream applications, especially for bioconversion. In this study, we demonstrate a hybrid biological-chemical conversion process for PE, converting its decomposition products, namely short-chain diacids, into a monomer, β-keto-δ-lactone (BKDL), for highly recyclable polydiketoenimine plastics using engineered <em>Corynebacterium glutamicum</em>. Since BKDL synthesis requires a substantial supply of malonyl-CoA, we employed an alternative biosynthesis pathway that leverages <em>C. glutamicum</em>'s natural proficiency in amino acid production. We optimized this pathway <em>in vivo</em> by minimizing carbon loss to CO₂ and byproducts, improving the transporter system, and maximizing co-factor regeneration. Furthermore, we co-optimized the PE deconstruction process to produce predominantly C4 to C6 diacids and integrated three catabolic pathways into the engineered strain to enhance diacid utilization, maximizing the carbon conversion from PE. Finally, an engineered polyketide synthase was introduced into <em>C. glutamicum</em> to enable BKDL synthesis. This work demonstrates the potential of a chemo-biological hybrid strategy for recycling plastic waste, highlighting its promise in addressing environmental challenges and promoting sustainable materials.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 106-116"},"PeriodicalIF":6.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586287","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 Corynebacterium glutamicum for highly selective production of 5-hydroxyvaleric acid","authors":"Yu Jung Sohn ,&nbsp;Hee Taek Kim ,&nbsp;Minsoo Kang ,&nbsp;Jina Son ,&nbsp;Kyungmoon Park ,&nbsp;Ki Jun Jeong ,&nbsp;Sang Yup Lee ,&nbsp;Jeong Chan Joo ,&nbsp;Si Jae Park","doi":"10.1016/j.ymben.2025.03.002","DOIUrl":"10.1016/j.ymben.2025.03.002","url":null,"abstract":"<div><div>The biosynthesis of 5-hydroxyvaleric acid (5-HV) from glucose via the l-lysine degradation pathway cocurrently generates by-products, including l-lysine, 5-aminovaleric acid (5-AVA), and glutaric acid (GTA), which are closely interconnected with the 5-HV biosynthesis pathway. This study focuses on developing a highly selective 5-HV production system in <em>Corynebacterium glutamicum</em>. Initial strategies, such as using sorbitol as a co-substrate, deleting the endogenous GTA biosynthesis pathway, and incorporating a GTA recycling system, were insufficient to achieve selectivity. To address this, a combination of strategies was implemented, including deletion of the endogenous GTA biosynthesis pathway, incorporation of a GTA recycling pathway, removal of the l-lysine exporter gene (<em>lysE</em>), and integration of a l-lysine conversion module. These modifications synergistically enhanced 5-HV selectivity. The final engineered strain, which lacked <em>lysE</em> and <em>gabD2</em> genes and overexpressed the 5-HV biosynthesis and GTA recycling modules, achieved 88.23 g/L of 5-HV in fed-batch fermentation. By-product levels were significantly reduced to 3.28 g/L of GTA, 1.16 g/L of 5-AVA, and no detectable l-lysine. With this highly selective 5-HV biosynthesis system, δ-valerolactone (DVL) was synthesized via acid treatment of microbially produced 5-HV, achieving a 65% conversion efficiency. This approach presents a more environmentally friendly and sustainable method for producing DVL, a valuable C5 solvent with industrial applications.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 33-42"},"PeriodicalIF":6.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579838","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":"The halo of future bio-industry based on engineering Halomonas","authors":"Xu Yan ,&nbsp;Jiale Wang ,&nbsp;Rou Wen ,&nbsp;Xinyu Chen ,&nbsp;Guo-Qiang Chen","doi":"10.1016/j.ymben.2025.03.001","DOIUrl":"10.1016/j.ymben.2025.03.001","url":null,"abstract":"<div><div>The utilization of microorganisms to transform biomass into biofuels and biochemicals presents a viable and competitive alternative to conventional petroleum refining processes. <em>Halomonas</em> species are salt-tolerant and alkaliphilic, endowed with various beneficial properties rendering them as contamination resistant platforms for industrial biotechnology, facilitating the commercial-scale production of valuable bioproducts. Here we summarized the metabolic and genomic engineering approaches, as well as the biochemical products synthesized by <em>Halomonas</em>. Methods were presented for expanding substrates utilization in <em>Halomonas</em> to enhance its capabilities as a robust workhorse for bioproducts. In addition, we briefly reviewed the Next Generation Industrial Biotechnology (NGIB) based on <em>Halomonas</em> for open and continuous fermentation. In particular, we proposed the industrial attempts from <em>Halomonas</em> chassis and the rising prospects and essential strategies to enable the successful development of <em>Halomonas</em> as microbial NGIB manufacturing platforms.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"90 ","pages":"Pages 16-32"},"PeriodicalIF":6.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573454","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}