Current opinion in biotechnology最新文献

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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 : 2025-12-01 Epub 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":"2025-12-01","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
Programmable probiotics as next-generation living therapeutics: bridging synthetic biology and precision medicine 可编程益生菌作为下一代生命疗法:连接合成生物学和精准医学。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.copbio.2025.103375
Na Li , Lijie Yin , Jia Wang , Jing Zhang , Yaojun Tong
{"title":"Programmable probiotics as next-generation living therapeutics: bridging synthetic biology and precision medicine","authors":"Na Li ,&nbsp;Lijie Yin ,&nbsp;Jia Wang ,&nbsp;Jing Zhang ,&nbsp;Yaojun Tong","doi":"10.1016/j.copbio.2025.103375","DOIUrl":"10.1016/j.copbio.2025.103375","url":null,"abstract":"<div><div>Engineered probiotics are rapidly redefining what’s possible for living therapeutics. Instead of acting passively, these microbes can now home to disease sites, sense local signals, and deliver precisely the therapeutic activities our patients need — directly <em>in situ</em> and for extended periods. With the help of modular genetic circuits, synthetic biology is transforming once-commensal bacteria into sophisticated, programmable medicines. In this review, we highlight how these designer microbes are tackling inflammatory bowel disease, metabolic conditions, and cancer, and we offer a critical look at the strategies underpinning their safety, efficacy, and clinical translation. We also discuss the translational bottlenecks, such as biocontainment, regulatory complexity, and microbiome variability, that must be overcome as these living medicines move from concept toward routine clinical use. Ultimately, programmable probiotics stand poised to reshape pharmaceutical biotechnology, sitting squarely at the intersection of microbiology, engineering, and precision medicine.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103375"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444081","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 : 2025-12-01 Epub 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":"2025-12-01","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
Designed dietary fibers: engineering carbohydrate structure for precision modulation of the human gut microbiome 设计膳食纤维:工程碳水化合物结构,精确调节人类肠道微生物群
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-10-23 DOI: 10.1016/j.copbio.2025.103371
Marcelo Iñaki Guerrero Montalván , Mariana Guzmán Sánchez , Victoria Gutierrez , Yunus E Tunçil , Stephen R Lindemann
{"title":"Designed dietary fibers: engineering carbohydrate structure for precision modulation of the human gut microbiome","authors":"Marcelo Iñaki Guerrero Montalván ,&nbsp;Mariana Guzmán Sánchez ,&nbsp;Victoria Gutierrez ,&nbsp;Yunus E Tunçil ,&nbsp;Stephen R Lindemann","doi":"10.1016/j.copbio.2025.103371","DOIUrl":"10.1016/j.copbio.2025.103371","url":null,"abstract":"<div><div>The human colonic microbiota exerts a profound influence on health, mediated by highly specific relationships among dietary fiber structures and microbial degraders. Systematic control of fiber structure offers opportunities to engineer microbiota-targeted interventions with increasing precision. Here, we examine the evolution of <em>designed dietary fibers —</em> biotechnologically produced oligosaccharides or polysaccharides synthesized <em>de novo</em> or naturally occurring polysaccharides intentionally modified post-extraction for their fine physical or chemical structures to influence gut microbiome. We propose a hierarchical framework to classify these fibers based on the degree of fine structure control, highlight current strategies for carbohydrate modification approaches, and discuss emerging directions for the field. Despite recent advances, much potential remains unrealized for the rational, reproducible design of microbiome-targeted fibers.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103371"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358342","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 : 2025-12-01 Epub 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":"2025-12-01","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
Molecules to medicine: advances in metabolomics for natural product drug discovery 分子到医学:天然产物药物发现的代谢组学进展
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-10-31 DOI: 10.1016/j.copbio.2025.103373
Victoria Deleray , Pieter C Dorrestein , Nicole E Avalon
{"title":"Molecules to medicine: advances in metabolomics for natural product drug discovery","authors":"Victoria Deleray ,&nbsp;Pieter C Dorrestein ,&nbsp;Nicole E Avalon","doi":"10.1016/j.copbio.2025.103373","DOIUrl":"10.1016/j.copbio.2025.103373","url":null,"abstract":"<div><div>Recent advances in metabolomics are accelerating natural product (NP) drug discovery. NPs possess diverse biological relevance and comprise a significant portion of our modern pharmacopeia. We highlight studies from the past two years with innovative discovery techniques, ranging from small sample analyses to large-scale data-driven approaches. We focus on nuclear magnetic resonance- and mass spectrometry-based metabolomics for their broad use and greatest advancements in the field. We highlight strategies that utilize computational tools to enable prioritization of samples based on structural novelty, cross-referencing structural data with bioactivity, and the development of innovative annotation techniques that surpass common library matching methods. We also look at the trajectory of metabolomic discovery of NPs over the last decade to inform how these platforms may further evolve. The goal is to enhance the likelihood and improve the efficiency of discovering NPs with pharmaceutical potential, while strategically harnessing data in order to reduce rediscovery and methodological redundancy.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103373"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412718","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
Resolving misconceptions and constraints in growth-coupled bioproduction 解决生长耦合生物生产中的误解和限制
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-11-21 DOI: 10.1016/j.copbio.2025.103388
Lena M Hümmler , Stefan Hristov , Lucas Hille , Elad Noor , Steffen N Lindner
{"title":"Resolving misconceptions and constraints in growth-coupled bioproduction","authors":"Lena M Hümmler ,&nbsp;Stefan Hristov ,&nbsp;Lucas Hille ,&nbsp;Elad Noor ,&nbsp;Steffen N Lindner","doi":"10.1016/j.copbio.2025.103388","DOIUrl":"10.1016/j.copbio.2025.103388","url":null,"abstract":"<div><div>Growth-coupled bioproduction (GCBP) is a metabolic engineering approach that introduces an obligatory dependency between metabolic activity and production, ensuring a high minimal yield and genetic stability. Here, product yield is primarily limited by pathway constraints, which can be overcome by further metabolic engineering. However, misconceptions persist in understanding GCBP among metabolic and process engineers. Contrary to misperceptions, yield is not stoichiometrically constrained by the growth-restoring enzymatic step, cell division is nonessential for production, and GCBP is compatible with multistage fermentation processes. Finally, GCBP addresses reduced production arising from genetic drift caused by population heterogeneity. Still, challenges remain: the lack of metabolic engineering tools for nonmodel organisms, limited <em>in silico</em> design capabilities, and the existence of uncharacterized metabolism. Nevertheless, by setting a high minimal stoichiometric yield, GCBP facilitates continuous bioproduction. Overall, integrating GCBP with metabolic engineering and improved computational design has the potential to reshape industrial biotechnology toward robust and efficient bioproduction.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103388"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576144","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 : 2025-12-01 Epub 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":"2025-12-01","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
Engineering metabolism of Saccharomyces cerevisiae for production of chemicals 用于化工生产的酿酒酵母菌工程代谢。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-11-18 DOI: 10.1016/j.copbio.2025.103387
Yi Yu , Xiaoying Fu , Jinmiao Hu , Jens Nielsen , Shuobo Shi
{"title":"Engineering metabolism of Saccharomyces cerevisiae for production of chemicals","authors":"Yi Yu ,&nbsp;Xiaoying Fu ,&nbsp;Jinmiao Hu ,&nbsp;Jens Nielsen ,&nbsp;Shuobo Shi","doi":"10.1016/j.copbio.2025.103387","DOIUrl":"10.1016/j.copbio.2025.103387","url":null,"abstract":"<div><div>The sustainable production of chemicals from renewable, nonedible biomass has become crucial to address environmental challenges like climate change and resource depletion caused by fossil resource dependence. <em>Saccharomyces cerevisiae</em> has emerged as a versatile microbial chassis for industrial bioproduction of chemicals, with engineered breakthroughs in central carbon metabolism, lipid metabolism, and terpenoid metabolism. This review examines three transformative paradigms: (1) optimizing metabolic flux and redirecting yeast pathways for chemical biosynthesis (e.g. farnesene), (2) enhancing yeast robustness to improve biomass and biochemical production under fermentation stresses (e.g. succinic acid), and (3) expanding feedstock flexibility through engineered substrate assimilation (e.g. ethanol). These examples pave the way for producing sustainable chemicals. We also discuss future challenges and propose AI (Artificial Intelligence)-driven design tools, CRISPR-based genome editing, and integrated biological-chemical hybrid processes as next-generation solutions to advance a yeast-mediated circular bioeconomy.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103387"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556428","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
Building trust in automated experimentation: uncertainty quantification in the era of high-throughput biolabs 在自动化实验中建立信任:高通量生物实验室时代的不确定度量化。
IF 7 2区 工程技术
Current opinion in biotechnology Pub Date : 2025-12-01 Epub Date: 2025-11-13 DOI: 10.1016/j.copbio.2025.103382
Wolfgang Wiechert , Laura M Helleckes , Katharina Nöh
{"title":"Building trust in automated experimentation: uncertainty quantification in the era of high-throughput biolabs","authors":"Wolfgang Wiechert ,&nbsp;Laura M Helleckes ,&nbsp;Katharina Nöh","doi":"10.1016/j.copbio.2025.103382","DOIUrl":"10.1016/j.copbio.2025.103382","url":null,"abstract":"<div><div>Uncertainty quantification (UQ) is central to data analytics, particularly in the life sciences, where experiments are often affected by significant measurement noise. In emerging automated high-throughput biolabs, such as biofoundries, parallel cultivation systems, and smart analytics platforms, UQ should be a built-in feature rather than an optional add-on. These environments pose a unique challenge: robotic liquid handling must be combined with miniaturized biochemical analytics (including omics), process monitoring, online data analytics, and digital control. Although traditional UQ methods from classical and computational statistics remain valid and applicable, integrating them into highly parallelized experimental and digital workflows presents new challenges. These include data preprocessing, model-based data integration, decision-making, and experimental control. In this review, we examine the emerging demands on UQ in automated experimentation and survey recent frameworks, strategies, and computational tools designed to address them.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103382"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523021","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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