{"title":"Molecular machines from individuals to swarms","authors":"Bin Wang , Yuan Lu","doi":"10.1016/j.copbio.2025.103400","DOIUrl":"10.1016/j.copbio.2025.103400","url":null,"abstract":"<div><div>Molecular machines convert physical and chemical energy into effective mechanical work, and have made significant progress as tools capable of micro- and nano-scale smart manipulation in fields such as medicine, catalysis, and materials. However, functional limitations hinder the rapid iteration of molecular machines toward practical applications. This requires not only the individual design of molecular machines to achieve more efficient performance in diverse systems but also the cooperation of molecular machines through a swarm to integrate spatial and temporal aspects, thereby scaling up molecular-scale deformations to macroscopic work. In this review, we discuss the latest achievements in individual and swarm design of molecular machines, address existing challenges, and provide insights into the future development of these machines.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103400"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721515","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}
Laura Marie Helleckes , Sebastian Putz , Kshitiz Gupta , Matthias Franzreb , Hector Garcia Martin
{"title":"Perspectives for artificial intelligence in bioprocess automation","authors":"Laura Marie Helleckes , Sebastian Putz , Kshitiz Gupta , Matthias Franzreb , Hector Garcia Martin","doi":"10.1016/j.copbio.2025.103392","DOIUrl":"10.1016/j.copbio.2025.103392","url":null,"abstract":"<div><div>Recent advances in artificial intelligence (AI) have rapidly changed the lab automation landscape, promoting self-driving laboratories (SDLs) that enable autonomous scientific discovery. These trends are increasingly applied in bioprocess development, yet bioprocessing faces unique challenges — biological complexity, regulatory and safety requirements, and multiscale experimentation — that distinguish it from other automation domains. Rather than pursuing full autonomy, we foresee that hybrid SDLs, combining AI-driven decision-making with sustained human oversight, represent the most practical near-term trajectory. This review examines three interconnected perspectives: (i) hybrid human–machine decision-making for bioprocessing; (ii) laboratory design considerations in the era of AI; and (iii) scale-up challenges when transitioning from screening to manufacturing. We highlight critical gaps in data standardization and the required community efforts necessary to realize autonomous bioprocess innovation.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103392"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616655","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":"Harnessing plant natural products for enhanced biotic stress resistance","authors":"Yoshiahu Goldstein, Guy Polturak","doi":"10.1016/j.copbio.2025.103432","DOIUrl":"10.1016/j.copbio.2025.103432","url":null,"abstract":"<div><div>Plant natural products (PNPs) are specialized metabolites with diverse biological activities that are central to plant adaptation to biotic stresses. They act as chemical defenses against pathogens and pests, supporting plant survival under attack. Harnessing their potential as eco-friendly biopesticides requires a detailed understanding of their biosynthetic pathways and biological functions. This review highlights recent advances in the discovery and pathway elucidation of defensive PNPs and discusses strategies for their application through heterologous expression and enhanced <em>in planta</em> production.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103432"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972880","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}
Križan Jurinović, Merry Mitra, Rakesh Mukherjee, Thomas E Ouldridge
{"title":"Design of DNA strand displacement reactions","authors":"Križan Jurinović, Merry Mitra, Rakesh Mukherjee, Thomas E Ouldridge","doi":"10.1016/j.copbio.2025.103396","DOIUrl":"10.1016/j.copbio.2025.103396","url":null,"abstract":"<div><div>DNA strand displacement (SD) reactions are central to the operation of many synthetic nucleic acid systems, including molecular circuits, sensors, and machines. Over the years, a broad set of design frameworks has emerged to accommodate various functional goals, initial configurations, and environmental conditions. Nevertheless, key challenges persist, particularly in reliably predicting reaction kinetics. In contrast to reviews centred on network-level architectures, this article focuses on the design and analysis of individual SD reactions, highlighting kinetic mechanisms, structural determinants, and the current limits of predictive modelling. We identify promising innovations while analysing the factors that continue to hinder predictive accuracy. We conclude by outlining future directions for achieving more robust and programmable behaviour in DNA-based systems.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"97 ","pages":"Article 103396"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682219","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":"Large language model agents as experimental orchestrators in data-driven enzyme engineering","authors":"Yuan Gao , Lihao Fu , Tong Si","doi":"10.1016/j.copbio.2025.103376","DOIUrl":"10.1016/j.copbio.2025.103376","url":null,"abstract":"<div><div>Artificial intelligence (AI) has revolutionized computational enzyme design, but experimental validation remains a critical bottleneck. This perspective examines how large language model (LLM) agents bridge the gap between computational predictions and physical experimentation through intelligent orchestration of complex experimental workflows. Unlike traditional automation following rigid scripts, LLM-powered systems dynamically generate protocols, translate them into machine commands, coordinate resources, and adapt to experimental feedback in real-time. This short perspective covers multi-agent frameworks from recent implementations and presents case studies showcasing closed-loop design-build-test-learn iterations in enzyme engineering. These systems provide both standardization and flexibility needed to handle complex, context-dependent experimental decisions, potentially accelerating enzyme engineering while enhancing accessibility to sophisticated AI capabilities.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103376"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412717","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}
Catharine E Bosman , Luvuyo Tyhoda , Johann F Görgens , Kim M Trollope
{"title":"Building a lignin biofoundry: a review","authors":"Catharine E Bosman , Luvuyo Tyhoda , Johann F Görgens , Kim M Trollope","doi":"10.1016/j.copbio.2025.103377","DOIUrl":"10.1016/j.copbio.2025.103377","url":null,"abstract":"<div><div>Lignin, a complex biopolymer, holds significant promise for sustainable bioconversion into high-value products and chemicals; however, its recalcitrance, variable composition, and low degradation rates limit industrial application. Naturally sourced enzymes remain insufficient, and mature commercial solutions are scarce. Synthetic biology opens new avenues for lignin biotransformation, particularly through biofoundries that automate the ‘design-build-test-learn’ cycle. These platforms can integrate robotics, data-driven biology, and artificial intelligence to expedite ligninolytic enzyme development. By enabling high-throughput screening, directed evolution, and biosensor-guided selection, lignin-focused biofoundries present a transformative framework for overcoming current limitations. This review explores recent biotechnological advances and highlights the potential of biofoundries to unlock lignin’s untapped economic and environmental potential.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103377"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412716","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":"Architectures of emerging biofoundry platforms for synthetic biology","authors":"Yu Been Heo , Jun Sung Park , Han Min Woo","doi":"10.1016/j.copbio.2025.103379","DOIUrl":"10.1016/j.copbio.2025.103379","url":null,"abstract":"<div><div>Biofoundries are integrated, automated platforms that accelerate synthetic biology applications by facilitating high-throughput and labor-intensive experiments. They incorporate robotic systems, analytical instruments, and software for workflow design, execution, and data management, ensuring scalable and reproducible biological engineering. This review outlines the architectural foundations of biofoundries, emphasizing Robot-Assisted Modules (RAMs) that support modular and flexible workflow configurations from simple single-task units to complex, multi-workstation systems. Advances in software development, from compiler-level tools to high-level platforms, have further enhanced workflow design and system interoperability. We examine key synthetic biology applications, including DNA assembly, strain engineering, and pathway optimization, that benefit from automated and high-throughput operations. In parallel, performance evaluation metrics are being developed to guide implementation and optimization. Finally, the integration of artificial intelligence enables predictive modeling and iterative learning, laying the groundwork for self-driving laboratories that will support sustainable and distributed synthetic biology at scale.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103379"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412719","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":"Microfluidics meets cell-free systems: from molecular engineering to synthetic cells","authors":"Amogh K Baranwal, Sebastian J Maerkl","doi":"10.1016/j.copbio.2025.103384","DOIUrl":"10.1016/j.copbio.2025.103384","url":null,"abstract":"<div><div>Cell-free systems have emerged as a powerful platform for protein production, characterization, and bottom-up construction of artificial cells, offering direct control over biochemical environments. However, achieving high-throughput and iterative design–build–test cycles requires advanced strategies beyond conventional methods. Microfluidic technologies address these challenges by enabling miniaturization, automation, and exceptional control over reaction conditions. The integration of cell-free systems with microfluidics has unlocked new capabilities by enabling high-throughput assays, long-lived reactions in continuous-flow systems, and the generation of liposome-based artificial cells. This review highlights recent advances at this interface, focusing on microfluidic strategies for protein characterization, gene regulatory studies, and the bottom-up construction of artificial cells exhibiting life-like functions.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103384"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576299","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":"Molecular methods for high-throughput, multiplexed, and automated genome editing in prokaryotes and eukaryotes","authors":"Dominic Kösters , Jan Marienhagen","doi":"10.1016/j.copbio.2025.103381","DOIUrl":"10.1016/j.copbio.2025.103381","url":null,"abstract":"<div><div>Novel approaches to genome engineering are crucial to rapidly advance the capabilities of strain engineering and synthetic biology. With ongoing developments in DNA editing techniques, researchers have begun to engineer organisms at higher throughput and can now perform multiple genome modifications simultaneously. As laboratory automation becomes more accessible, workflows are being transferred to robot-assisted platforms, enabling large-scale and highly parallelized genome editing campaigns. These platforms play a key role in fully utilizing the potential of modern molecular biology tools. Here, we review recent developments in technologies for high-throughput, multiplexed, and automated strain engineering in prokaryotic and eukaryotic organisms.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103381"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462582","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}
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}