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Emerging strategies to enhance microbial natural product–based drug discovery 新兴战略加强微生物天然产物为基础的药物发现
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-10 DOI: 10.1016/j.copbio.2025.103369
Michael Madden , Conor Pulliam , Katherine Holandez-Lopez , Andrew Campbell , Jie Li
{"title":"Emerging strategies to enhance microbial natural product–based drug discovery","authors":"Michael Madden ,&nbsp;Conor Pulliam ,&nbsp;Katherine Holandez-Lopez ,&nbsp;Andrew Campbell ,&nbsp;Jie Li","doi":"10.1016/j.copbio.2025.103369","DOIUrl":"10.1016/j.copbio.2025.103369","url":null,"abstract":"<div><div>Natural products (NPs) have served as a major source of chemically novel, bioactive therapeutics for the treatment of various diseases. In recent years, NP discovery has benefited greatly from advancements in biotechnological fields. This review covers techniques and tools from 2022 to 2025 that have expanded NP discovery capabilities through gene-editing tools to activate silent biosynthetic genes, cell-free methods for NP production and diversification, as well as artificial intelligence and informatics tools for structure generation and correlational studies.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103369"},"PeriodicalIF":7.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Production of chemicals by metabolically engineered Escherichia coli 通过代谢工程改造的大肠杆菌生产化学物质。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-06 DOI: 10.1016/j.copbio.2025.103367
Gyudong Jang , Min-Jung Kim , Sang Yup Lee
{"title":"Production of chemicals by metabolically engineered Escherichia coli","authors":"Gyudong Jang ,&nbsp;Min-Jung Kim ,&nbsp;Sang Yup Lee","doi":"10.1016/j.copbio.2025.103367","DOIUrl":"10.1016/j.copbio.2025.103367","url":null,"abstract":"<div><div><em>Escherichia coli</em> is increasingly employed for chemical production, with its industrial competitiveness now depending on both the expansion of its molecular repertoire through first-in-class pathways and achieving best-in-class titer, rate, and yield (TRY). Recent milestones include the first demonstration of producing aromatic homopolyester and poly(ester amide)s from glucose using engineered <em>E. coli</em>. To optimally maximize TRY, systems metabolic engineering leverages diverse tools such as genome-scale CRISPRi/sRNA libraries, dynamic biosensors, and redox-balancing modules to optimally channel cellular resources toward product formation. In parallel, <em>in silico</em> tools support retrobiosynthetic pathway design, flux optimization, and enzyme engineering. By integrating first-in-class pathway construction with best-in-class TRY optimization, <em>E. coli</em> is poised to drive the next generation of sustainable, large-scale biomanufacturing. Overall, this review outlines representative achievements, strategic approaches, and emerging prospects, highlighting how recent advancements are positioning <em>E. coli</em> as a versatile and competitive chassis for sustainable production of value-added chemicals and materials.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103367"},"PeriodicalIF":7.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Strategies for engineering domesticated and undomesticated human microbes 驯化和未驯化人类微生物的工程策略。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-04 DOI: 10.1016/j.copbio.2025.103368
Dake Liu, Meng-Lun Hsieh, Yousong Ding
{"title":"Strategies for engineering domesticated and undomesticated human microbes","authors":"Dake Liu,&nbsp;Meng-Lun Hsieh,&nbsp;Yousong Ding","doi":"10.1016/j.copbio.2025.103368","DOIUrl":"10.1016/j.copbio.2025.103368","url":null,"abstract":"<div><div>Human-associated microbes hold immense therapeutic potential, yet most species remain undomesticated due to cultivation barriers and limited genetic tools. Recent advances in genetic engineering are overcoming these challenges, enabling the precise manipulation of both domesticated and previously intractable microbes. This review highlights established strategies for engineering domesticated strains, such as <em>Escherichia coli</em> Nissle 1917 and lactic acid bacteria, for diverse therapeutic applications. We also discuss emerging tools, including optimized transformation protocols for skin commensals and genome-editing approaches for <em>Clostridium</em> species and undomesticated <em>E. coli</em>, that address key barriers in non-model microbes and expand the potential of engineered microbiome therapeutics.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103368"},"PeriodicalIF":7.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering microbial exopolysaccharides for food applications. 食品用工程微生物胞外多糖。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.copbio.2025.103339
Jannis Broeker, Jochen Schmid
{"title":"Engineering microbial exopolysaccharides for food applications.","authors":"Jannis Broeker, Jochen Schmid","doi":"10.1016/j.copbio.2025.103339","DOIUrl":"10.1016/j.copbio.2025.103339","url":null,"abstract":"<p><p>Microbial exopolysaccharides for direct food applications remain rare due to significant financial and regulatory hurdles. However, exopolysaccharides without direct food approval have recently been employed in various indirect food-related uses. This review highlights microbial exopolysaccharides with strong potential for both direct and indirect food applications and outlines engineering strategies to optimize their biotechnological production. For sucrase-based polysaccharides, enzyme engineering aimed at controlling molecular weight has shown strong potential for generating novel functional properties. In the case of synthase-based polysaccharides, leveraging epimerases or exploiting the natural promiscuity of the synthase enzyme emerges as a particularly promising approach. For heteropolysaccharides, this review presents some rare examples of successful engineering and heterologous expression in chassis organisms, while also identifying key challenges that still limit efficient optimization.</p>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"95 ","pages":"103339"},"PeriodicalIF":7.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the prebiotic potential of polyphenols in gut health and metabolism. 揭示多酚在肠道健康和代谢中的益生元潜力。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1016/j.copbio.2025.103338
Katherine Petersen, Thomas J Mansell
{"title":"Unveiling the prebiotic potential of polyphenols in gut health and metabolism.","authors":"Katherine Petersen, Thomas J Mansell","doi":"10.1016/j.copbio.2025.103338","DOIUrl":"10.1016/j.copbio.2025.103338","url":null,"abstract":"<p><p>Polyphenols are a diverse class of plant metabolites with noted health benefits, such as antioxidant, anticancer, and antidiabetic effects. Recently, these compounds have gained interest for their ability to manipulate the composition of the human gut microbiome through distinct mechanisms, including microbial metabolism, enzymatic biotransformation, and antimicrobial effects. For example, many gut microbes express β-glucosidases or polyphenol catabolizing enzymes (PAZymes), which could enable the use of these compounds in competitive niches. This review explores recent research on the enzymes that interact with these substrates, the mechanisms by which polyphenols modulate the gut microbiome, and the use of polyphenolic compounds as next-generation prebiotics for the benefit of the human host.</p>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"95 ","pages":"103338"},"PeriodicalIF":7.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial overview: Microbial frontiers in environmental biotechnology 编辑概述：微生物在环境生物技术的前沿。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-10-01 DOI: 10.1016/j.copbio.2025.103366
Mari Winkler , George F. Wells
{"title":"Editorial overview: Microbial frontiers in environmental biotechnology","authors":"Mari Winkler ,&nbsp;George F. Wells","doi":"10.1016/j.copbio.2025.103366","DOIUrl":"10.1016/j.copbio.2025.103366","url":null,"abstract":"","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103366"},"PeriodicalIF":7.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unearth hidden terpenoids in plants by genome mining and synthetic biology 通过基因组挖掘和合成生物学挖掘植物中隐藏的萜类化合物
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-09-27 DOI: 10.1016/j.copbio.2025.103365
Weijia Cheng , Aohan Geng , Li Lu
{"title":"Unearth hidden terpenoids in plants by genome mining and synthetic biology","authors":"Weijia Cheng ,&nbsp;Aohan Geng ,&nbsp;Li Lu","doi":"10.1016/j.copbio.2025.103365","DOIUrl":"10.1016/j.copbio.2025.103365","url":null,"abstract":"<div><div>Plant terpenoids are a vital source of natural products, yet their discovery is often hindered by low abundance or cryptic expression. The integration of genome mining and synthetic biology has emerged as a transformative solution, enabling systematic discovery and characterization of novel terpenoid scaffolds across all major terpenoid classes, including triterpenes, sesterterpenes, diterpenes, and sesquiterpenes. This review highlights key advances achieved through genome-wide functional characterization of terpene synthases, combinatorial biosynthesis approaches, and scalable production systems for bioactivity evaluation. These integrated strategies have proven particularly valuable for uncovering hidden terpenoid diversity and studying naturally rare terpenoids in plants, significantly expanding the chemical space available for pharmaceutical development and drug discovery.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103365"},"PeriodicalIF":7.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From marsh to market: taming Vibrio natriegens for sustainable bioproduction 从沼泽到市场：培育可持续生物生产所需的营养弧菌
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-09-12 DOI: 10.1016/j.copbio.2025.103353
Simona Della Valle , Anna Faber , Roland J Politan , Suman Lama , Georg Fritz
{"title":"From marsh to market: taming Vibrio natriegens for sustainable bioproduction","authors":"Simona Della Valle ,&nbsp;Anna Faber ,&nbsp;Roland J Politan ,&nbsp;Suman Lama ,&nbsp;Georg Fritz","doi":"10.1016/j.copbio.2025.103353","DOIUrl":"10.1016/j.copbio.2025.103353","url":null,"abstract":"<div><div>As the fastest-growing bacterium known to date, <em>Vibrio natriegens</em> is rapidly emerging as a promising chassis for biotechnology. Here, we explore its development towards sustainable bioproduction. Several innate traits underpin this progress, including the ability to metabolise next-generation feedstocks such as formate, acetate, and glycerol, as well as its halotolerance. Recent advances in genome engineering, synthetic biology tools, and systems-level analyses have enabled the application of <em>V. natriegens</em> in increasingly efficient bioprocesses. Yet, important constraints persist, particularly in achieving high product yields and processing recalcitrant substrates. We propose that these limitations can be addressed through a systems biotechnology approach, coupling strain and process engineering to guide the rational optimisation of <em>V. natriegens</em> for scalable, next-generation biomanufacturing.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103353"},"PeriodicalIF":7.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eubacterium limosum as a biocatalyst for sustainable methanol bioconversion 石灰真杆菌作为可持续甲醇生物转化的生物催化剂。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-09-10 DOI: 10.1016/j.copbio.2025.103354
Jiyun Bae , Hyunwoo Jung , Byung-Kwan Cho
{"title":"Eubacterium limosum as a biocatalyst for sustainable methanol bioconversion","authors":"Jiyun Bae ,&nbsp;Hyunwoo Jung ,&nbsp;Byung-Kwan Cho","doi":"10.1016/j.copbio.2025.103354","DOIUrl":"10.1016/j.copbio.2025.103354","url":null,"abstract":"<div><div><em>Eubacterium limosum</em> is an acetogenic bacterium capable of utilizing one-carbon substrates — CO<sub>2</sub>, CO, formate, and methanol — while producing valuable reduced compounds, including butyrate and hexanoate. Its broad substrate range and robust methanol utilization make it a promising platform for sustainable methanol bioconversion. Recent advances in genetic and analytical tools have enabled comprehensive systems-level characterization and metabolic engineering. Additionally, methanol mixotrophy strategies have significantly improved energy availability and product yields. This review examines current progress in <em>E. limosum</em> research, focusing on genetic tool development, methanol-based biochemical production, and mixotrophy implementation. We conclude by outlining future directions for enhancing strain performance and establishing <em>E. limosum</em> as an industrial biocatalyst for methanol valorization.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103354"},"PeriodicalIF":7.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring interactions in microbial communities 探索微生物群落的相互作用
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-09-09 DOI: 10.1016/j.copbio.2025.103352
Loïc Marrec , Gabriela Bravo-Ruiseco , Xingjian Zhou , Adedamola G Daodu , Karoline Faust
{"title":"Exploring interactions in microbial communities","authors":"Loïc Marrec ,&nbsp;Gabriela Bravo-Ruiseco ,&nbsp;Xingjian Zhou ,&nbsp;Adedamola G Daodu ,&nbsp;Karoline Faust","doi":"10.1016/j.copbio.2025.103352","DOIUrl":"10.1016/j.copbio.2025.103352","url":null,"abstract":"<div><div>Most microbial ecosystems cannot be understood without quantifying ecological interactions between their member species. Given the challenges of comprehensively resolving interactions experimentally, a range of prediction methods was developed. Here, we review genome-based prediction methods in particular and discuss their strengths and weaknesses. We then cover different experimental designs to explore microbial interactions and introduce methods to infer interaction signs and strengths from experimental data. Despite the range of available methods to study microbial interactions <em>in silico</em> and <em>in vitro</em>, interactions in a spatial context are still underexplored, and we lack comprehensive interaction databases, which are important gaps to fill in the future.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103352"},"PeriodicalIF":7.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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