Ji Hun Kim , Jae Heon Kim , Seong Do Kim , Haseong Kim , Byung-Kwan Cho
{"title":"Recent advances in AI-enabled automation of DNA assembly in biofoundries","authors":"Ji Hun Kim , Jae Heon Kim , Seong Do Kim , Haseong Kim , Byung-Kwan Cho","doi":"10.1016/j.copbio.2025.103386","DOIUrl":"10.1016/j.copbio.2025.103386","url":null,"abstract":"<div><div>Biofoundries are transforming synthetic biology, with the DNA assembly workflow being critical for successful biofoundry operation. This review examines recent advances in automated DNA assembly strategies for biofoundry, focusing on three key perspectives. First, we discuss emerging platforms ranging from high-throughput and highly efficient systems to affordable and accessible solutions. Second, we explore how standardized design tools enable seamless interoperability across diverse biofoundries, facilitating protocol sharing and reproducibility. Third, we analyze the integration of machine learning into assembly workflows, in which AI-driven systems dynamically optimize protocols, diagnose failures, and close the DBTL loop through real-time learning. These convergent advances are establishing a new paradigm in which experiments continuously improve through iteration, promising to accelerate both fundamental research and industrial applications.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103386"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462581","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}
{"title":"Exploring interactions in microbial communities","authors":"Loïc Marrec , Gabriela Bravo-Ruiseco , Xingjian Zhou , Adedamola G Daodu , 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":"2025-12-01","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}
{"title":"Eubacterium limosum as a biocatalyst for sustainable methanol bioconversion","authors":"Jiyun Bae , Hyunwoo Jung , 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":"2025-12-01","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}
{"title":"Unearth hidden terpenoids in plants by genome mining and synthetic biology","authors":"Weijia Cheng , Aohan Geng , 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":"2025-12-01","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}
Haoyu Wang , Fan Bai , Hongzhong Lu , Yongjin J Zhou
{"title":"Understanding methanol metabolism through systems biology: advances and future perspectives","authors":"Haoyu Wang , Fan Bai , Hongzhong Lu , Yongjin J Zhou","doi":"10.1016/j.copbio.2025.103370","DOIUrl":"10.1016/j.copbio.2025.103370","url":null,"abstract":"<div><div>Methanol represents a promising sustainable one-carbon (C1) feedstock for biomanufacturing. However, limitations arising from cytotoxicity and incomplete metabolic understanding have resulted in low production efficiencies and constraining industrial applications. Recent systems biology approaches, including multi-omics and computational modeling, have significantly advanced our knowledge of microbial methanol metabolism. Here, we first summarize recent methodological progress in systems biology applied to methanol metabolism studies. Secondly, we highlight novel insights into understanding methanol metabolism by applying systems biology approaches in natural and synthetic methylotrophic microorganisms. Finally, we discuss the challenges and future perspectives for systems biology studies of methanol metabolism in yeast.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103370"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291442","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}
Aukse Gaizauskaite , Emma E. Crean , Imre Banlaki , Jan L. Kalkowski , Henrike Niederholtmeyer
{"title":"Controlled protein synthesis and spatial organisation in microfluidic environments","authors":"Aukse Gaizauskaite , Emma E. Crean , Imre Banlaki , Jan L. Kalkowski , Henrike Niederholtmeyer","doi":"10.1016/j.copbio.2025.103389","DOIUrl":"10.1016/j.copbio.2025.103389","url":null,"abstract":"<div><div>Performing cell-free expression (CFE) in tailored microfluidic environments is a powerful tool to investigate the organisation of biosystems from molecular to multicellular scales. While cell-free transcription–translation systems simplify and open up cellular biochemistry for manipulation, microfluidics enables miniaturisation and precise control over geometries and reaction conditions. In this review, we highlight the benefits of combining microfluidics with CFE reactions for the study and engineering of molecular functions and the construction of life-like systems from nonliving components. By defining spatial organisation at different scales and sustaining nonequilibrium conditions, microfluidic environments play a key role in the quest to ‘boot up’ the biochemistry of life.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103389"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525767","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}
{"title":"Whole-cell and cell-free biosensor-driven metabolic engineering","authors":"Jiho Seok, Mark P Styczynski","doi":"10.1016/j.copbio.2025.103385","DOIUrl":"10.1016/j.copbio.2025.103385","url":null,"abstract":"<div><div>Metabolic engineering employs microbial cell factories to produce high-value products from low-cost feedstocks. Designing, optimizing, and evaluating biosynthetic pathways in microbial cell factories is essential, yet these processes remain time- and labor-intensive. Biosensors help metabolic engineers address this challenge by converting target metabolite concentrations into observable outputs, enabling efficient assessment of microbial production. Whole-cell biosensors, which operate within living microorganisms, and cell-free biosensors, which function independently of cell growth using transcription–translation machinery, have contributed to microbial biosynthesis optimization through distinct approaches. This review summarizes recent advances in biosensor-driven metabolic engineering facilitated by whole-cell and cell-free biosensors<strong>.</strong></div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103385"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556437","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}
Nora Junker , Sara-Sophie Poethe , Volker F. Wendisch
{"title":"Aromatic compound production by Corynebacterium glutamicum: unified strategies at the core and diversity by extension","authors":"Nora Junker , Sara-Sophie Poethe , Volker F. Wendisch","doi":"10.1016/j.copbio.2025.103372","DOIUrl":"10.1016/j.copbio.2025.103372","url":null,"abstract":"<div><div>Aromatic compounds are an important class of natural substances with a wide range of physiological functions and, thus, applications in the food, feed, fine chemical, and plastics industries or as pharmaceuticals. As a prime player in industrial amino acid production, <em>C. glutamicum</em> is an ideal host to engineer the shikimate pathway for <em>de novo</em> biosynthesis of aromatic amino acids (AAAs) and derived arenes and heteroarenes. Recently, metabolic engineering strategies in this regard have converged, and potent AAA-producing strains have been developed. Three trends that will further expedite the field will be discussed: the use of alternative substrates, biofoundry approaches, and pathway extensions towards specialized metabolites with sought-after medical relevance.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103372"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358341","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}
Felix M Hubert , Anna C Love , Tian Lan , Hannah K Bone , Bradley S Moore
{"title":"Recent innovations in cannabinoid chemistry, biology, and biosynthesis","authors":"Felix M Hubert , Anna C Love , Tian Lan , Hannah K Bone , Bradley S Moore","doi":"10.1016/j.copbio.2025.103378","DOIUrl":"10.1016/j.copbio.2025.103378","url":null,"abstract":"<div><div><em>Cannabis sativa</em> and related plants are recognized for their psychoactive and therapeutic effects due to the unique molecules they produce, including phytocannabinoids. Beyond the major phytocannabinoids Δ⁹-tetrahydrocannabinol and cannabidiol, research on ‘minor cannabinoids’ has revealed new biological properties, motivating alternative production methods for these low-abundance molecules. Advances in asymmetric synthetic methods have enabled access to structurally complex cannabinoids and analogs. In tandem, synthetic biology approaches, including heterologous pathway reconstruction and functionally analogous enzyme discovery, have expanded the biosynthetic toolkit, delivering rare and novel cannabinoids at increasing scale. Here, we summarize the latest insights into cannabinoid pharmacology, synthetic chemistry innovations, and engineered production strategies, underscoring how feedback across disciplines is reshaping access to and understanding of minor cannabinoids.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103378"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462578","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}
Junyu Chen , Nilmani Singh , Jingxia Lu , Stephan T. Lane , Huimin Zhao
{"title":"Artificial intelligence–powered biofoundries for protein engineering and metabolic engineering","authors":"Junyu Chen , Nilmani Singh , Jingxia Lu , Stephan T. Lane , Huimin Zhao","doi":"10.1016/j.copbio.2025.103380","DOIUrl":"10.1016/j.copbio.2025.103380","url":null,"abstract":"<div><div>Synthetic biology is rapidly evolving through the integration of artificial intelligence (AI) and automated biofoundries. This convergence accelerates the design–build–test–learn cycle, shifting protein engineering and metabolic engineering from labor-intensive manual experimentation to autonomous experimentation. This review summarizes recent advances in workflow development, AI models, and their integration with biofoundries for automated or autonomous protein engineering and metabolic engineering. Particularly, we highlight the potential of AI-powered biofoundries for accelerated scientific discovery and innovation in synthetic biology.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103380"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451201","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}