Kate Collins , Claire E Stanley , Thomas E Ouldridge
{"title":"Biochemical surface patterning in microfluidic devices","authors":"Kate Collins , Claire E Stanley , Thomas E Ouldridge","doi":"10.1016/j.copbio.2025.103390","DOIUrl":"10.1016/j.copbio.2025.103390","url":null,"abstract":"<div><div>The capacity to pattern biomolecules within microfluidic devices expands the scope of microfluidic technologies. In such patterned systems, surface-bound components remain localized, while the microfluidic network supplies reagents and removes waste products. This approach has enabled continuous protein expression from patterned DNA, chemical synthesis from immobilized enzymes, and cell capture assays. Here, we review methods to pattern surfaces within microfluidic devices. Patterns may be printed before or after the device is assembled; pre-bonding methods are compatible with well-established open-surface patterning protocols but present challenges for device bonding and alignment. Conversely, post-bonding methods are compatible with standard bonding procedures but rely on less established, sequential patterning protocols. Future progress will require consistent reporting of pattern signal and noise relative to controls.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103390"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525753","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}
Ziyue Meng , Dongliang Ma , Ning He , Yinghua Lu , Mingfeng Cao
{"title":"Expanding the frontiers of microbial biosynthesis with synthetic microbial communities","authors":"Ziyue Meng , Dongliang Ma , Ning He , Yinghua Lu , Mingfeng Cao","doi":"10.1016/j.copbio.2025.103351","DOIUrl":"10.1016/j.copbio.2025.103351","url":null,"abstract":"<div><div>Advances in synthetic biology have extended microbial engineering to programmable microbial communities. Through rational pathway partitioning and well-defined microbial interactions, synthetic microbial communities mitigate limitations in monocultures such as metabolic burden, pathway inhibition, and byproducts accumulation. Featuring division of labor, synthetic microbial communities broaden system metabolic capabilities and enable efficient biosynthesis of complex chemicals, therefore expanding the frontiers of microbial biosynthesis. Here, we review recent progress in synthetic microbial communities. We discuss advantages and functions of synthetic microbial communities and propose a design framework, highlighting population control through microbial interactions. Challenges and future perspectives are addressed as well.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103351"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917857","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}
Gang Zhang , Zongchao Zuo , Jingzhi Wang , Ningqiang Gong , Xing-Jie Liang
{"title":"Ionizable lipids empowered with artificial intelligence for mRNA delivery","authors":"Gang Zhang , Zongchao Zuo , Jingzhi Wang , Ningqiang Gong , Xing-Jie Liang","doi":"10.1016/j.copbio.2025.103383","DOIUrl":"10.1016/j.copbio.2025.103383","url":null,"abstract":"<div><div>Ionizable lipids are the most significant component of lipid nanoparticles and govern the ability to deliver mRNA <em>in vitro</em> and <em>in vivo</em>. Traditional development methods for ionizable lipids depend on the labor-intensive multistep synthesis and empirical screening processes, which are costly and time-consuming. Empowering ionizable lipid development with artificial intelligence (AI) can overcome these limitations. With AI robots, all the synthesis and screening processes can almost be done automatically. With machine learning models, we can use datasets to train these models to predict novel ionizable lipids of good performance. With a self-driving lab, all the development processes before <em>in vivo</em> testing can be automated. With AI, the development of ionizable lipids is bound to be greatly revolutionized.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103383"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462580","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}
Peter H Winegar , Maria CT Astolfi , Sara F Holm , Graham A Hudson , Jay D Keasling
{"title":"Advances in the microbial biosynthesis of therapeutic terpenoids","authors":"Peter H Winegar , Maria CT Astolfi , Sara F Holm , Graham A Hudson , Jay D Keasling","doi":"10.1016/j.copbio.2025.103374","DOIUrl":"10.1016/j.copbio.2025.103374","url":null,"abstract":"<div><div>Terpenoid natural products and their derivatives exhibit bioactivity that is utilized in FDA-approved drugs and candidates for future drugs; however, the widespread utilization of terpenoids has been limited by complex, low-yielding native biosyntheses and chemical syntheses. Microbial total/semi-biosynthesis of natural and new-to-nature terpenoids from sustainable feedstocks is scalable and can achieve economically viable cost targets. Herein, this review describes foundational advances in synthetic biology and metabolic engineering as exemplified by efforts to biosynthesize prominent terpenoids (i.e. artemisinin, taxol, vinblastine, QS-21, and cyclopamine) in engineered microorganisms (e.g. <em>Escherichia coli</em> and <em>Saccharomyces cerevisiae</em>). Emerging methods that accelerate microbial biosynthesis campaigns (i.e. automation, machine learning, artificial intelligence, and combinatorial screening) are then discussed.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"96 ","pages":"Article 103374"},"PeriodicalIF":7.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400159","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":"Synthetic approaches to enhance biological carbon capture","authors":"Zhiyi Li , David L Lanster , Ahmed H Badran","doi":"10.1016/j.copbio.2025.103350","DOIUrl":"10.1016/j.copbio.2025.103350","url":null,"abstract":"<div><div>Biologically driven strategies to remove carbon dioxide from the atmosphere are gaining traction as long-term means for atmospheric correction. Many ongoing research efforts focus on enhancing the Calvin<em>–</em>Benson<em>–</em>Bassham (CBB) cycle with notable focus on the rate-limiting enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), aiming to alter its catalytic efficiency, substrate specificity, or cognate regulatory pathways. Beyond these strategies, novel approaches to provide energy to the CBB cycle or synthetic pathways for <em>in vivo</em> autotrophy have opened the door to engineerable carbon-negative biosynthesis. Finally, recent complementary studies that go beyond the CBB cycle to develop entirely new carbon fixation pathways have shown promise in addressing bottlenecks in efficiency and scalability of natural systems. In this perspective, we highlight many of these recent efforts to develop synthetic biology and bioengineering frameworks aimed at improving carbon capture efficiency, biomass productivity, and sustainable energy integration in living systems.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"95 ","pages":"Article 103350"},"PeriodicalIF":7.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911861","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":"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}
{"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}
Michael G Resch , Alex Badgett , Jens O Krömer , Esteban Marcellin
{"title":"Upstream considerations for gas fermentation processes","authors":"Michael G Resch , Alex Badgett , Jens O Krömer , Esteban Marcellin","doi":"10.1016/j.copbio.2025.103337","DOIUrl":"10.1016/j.copbio.2025.103337","url":null,"abstract":"<div><div>Gas fermentation enables the production of fuels, chemicals, and foods from gaseous carbon sources and could serve as a technology for valorizing carbon that may otherwise be emitted to the atmosphere. In this review, we focus on upstream feedstock considerations: the supply of carbon and the supply of electrical power. Electrical power serves a dual role, providing both process energy and biochemical redox potential (via hydrogen or reduced intermediates). We define gas fermentation as bioprocesses involving gaseous feedstocks metabolized by microbes, distinct from microbial electrosynthesis. Trends in CO<sub>2</sub> point sources and low-carbon electricity systems are analyzed, highlighting opportunities and challenges for future deployment. This review synthesizes current knowledge and identifies key R&D priorities for process integration at industrial scale.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"95 ","pages":"Article 103337"},"PeriodicalIF":7.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722152","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}
Hannah S Zurier , Scott Banta , Dan M Park , David W Reed , Allison Z Werner
{"title":"Biotechnological solutions for critical mineral recovery from unconventional feedstocks","authors":"Hannah S Zurier , Scott Banta , Dan M Park , David W Reed , Allison Z Werner","doi":"10.1016/j.copbio.2025.103336","DOIUrl":"10.1016/j.copbio.2025.103336","url":null,"abstract":"<div><div>Secure and sustainable metal recovery from unconventional feedstocks is needed to meet the mineral demands of energy, defense, and electronic technologies. Here, we highlight the potential to leverage nature’s ability to extract and differentiate metal ions in biotechnologies that could become the next generation of mining and refining. We describe bulk and trace processes and then discuss the advances and opportunities of two key bioprocesses: microbially mediated solubilization of metal ions from solid matrices (termed ‘bioleaching’) and bio-based separation of solubilized ions via selective adsorption to proteins. Both biotechnologies have advantages such as reduced energy input for leaching low-grade feedstocks and reduced organic solvent demand for separating ions with similar physiochemical properties but require more development for industrial scale recovery from unconventional feedstocks. Innovation in biological science and engineering may bring timely solutions to key challenges toward recovering critical minerals from unconventional feedstocks.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"95 ","pages":"Article 103336"},"PeriodicalIF":7.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703549","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}