Yangyang Li , Guocheng Du , Jian Chen , Xueqin Lv , Long Liu
{"title":"Glycosyltransferases in human milk oligosaccharide synthesis: structural mechanisms and rational design","authors":"Yangyang Li , Guocheng Du , Jian Chen , Xueqin Lv , Long Liu","doi":"10.1016/j.copbio.2025.103315","DOIUrl":"10.1016/j.copbio.2025.103315","url":null,"abstract":"<div><div>Human milk oligosaccharides (HMOs) play a pivotal role in infant health through their multifunctional bioactive properties. Recent advances in synthetic biology have revolutionized microbial platforms for HMO biosynthesis, with glycosyltransferases (GTs) emerging as indispensable biocatalytic tools that drive enzymatic lactose glycosylation to generate diversified oligosaccharides. This review systematically analyzes GT structural biology, elucidating conserved domains and catalytic mechanisms through crystallographic studies. We summarize contemporary optimization strategies for enhancing GT functionality, including solubility enhancement, catalytic efficiency improvement, and substrate specificity engineering via structure-guided rational design. Emerging deep learning algorithms demonstrate transformative potential in GT modifications and <em>de novo</em> design, providing innovative solutions to overcome bottlenecks in industrial-scale HMO synthesis. These approaches establish a framework for the precision engineering of carbohydrate-active enzymes.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103315"},"PeriodicalIF":7.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923729","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":"Understanding and harnessing the complexity of interspecies interactions in acetogenic mixotrophic co-cultures","authors":"John D Hill, Eleftherios T Papoutsakis","doi":"10.1016/j.copbio.2025.103311","DOIUrl":"10.1016/j.copbio.2025.103311","url":null,"abstract":"<div><div>The core advantage of acetogens lies in their superior carbon management, achieved by engaging the Wood–Ljungdahl pathway to sequester CO₂ <em>in situ</em> and utilize exogenous CO₂. This advantage can be further exploited by coupling acetogens with other organisms in co-culture, leading to the increasingly explored concept of acetogenic co-cultures. We review and dissect schemes involving the co-fermentation of carbohydrates and exogenous gases, which present unique challenges and opportunities due to the nonlinearity of co-culture metabolic networks and complex, often unanticipated, interspecies interactions. The latter suggests that most, if not all, such co-cultures are mutualistic rather than commensalistic, contrary to previous assumptions. We discuss both fundamental and applied concepts, including co-culture stability and methods for quantitatively capturing population dynamics and interspecies interactions.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103311"},"PeriodicalIF":7.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927680","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":"Recent advances in microbial synthesis of polyphenols","authors":"Yuxiang Hong , Pornpatsorn Lertphadungkit , Yongkun Lv , Peng Xu","doi":"10.1016/j.copbio.2025.103308","DOIUrl":"10.1016/j.copbio.2025.103308","url":null,"abstract":"<div><div>Polyphenols are plant-derived secondary metabolites known for their antioxidants, anti-inflammatory, and antimicrobial properties, with flavonoids being the most structurally diverse and medically relevant subclass. Traditional plant extraction is limited by low abundance and difficulty in separating from analogs. Microbial synthesis has emerged as an alternative method to complement plant extraction. This review summarizes recent advancements in microbe-sourced polyphenols, especially flavonoids and related derivatives. Key strategies, including modular design, CRISPR-based optimization, co-culture, and dynamic regulatory systems, have been employed to enhance microbial factory production efficiency. Emerging artificial intelligence–driven computational modeling and pathway optimization hold significant promise for enhancing polyphenol biosynthesis. Taken together, microbial synthesis offers a scalable and sustainable alternative to plant extraction. The cost-effective production of polyphenols will expand their applications in pharmaceuticals, nutraceuticals, and food industry.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103308"},"PeriodicalIF":7.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903511","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}
William Gasparrini , Seung H Lee , Benjamin M Woolston
{"title":"Pathways to sustainability: a quantitative comparison of aerobic and anaerobic C1 bioconversion routes","authors":"William Gasparrini , Seung H Lee , Benjamin M Woolston","doi":"10.1016/j.copbio.2025.103310","DOIUrl":"10.1016/j.copbio.2025.103310","url":null,"abstract":"<div><div>One-carbon (C1) substrates are attractive feedstocks for biological upgrading as part of a circular, carbon-negative bioeconomy. Nature has evolved a diverse set of C1-trophs that use a variety of pathways. Additionally, intensive effort has recently been invested in developing synthetic C1 assimilation pathways. This complicated landscape presents the question: “What pathways should be used to produce what products from what C1 substrates?” To guide the selection, we calculate and compare maximal theoretical yields for a range of bioproducts from different C1 feedstocks and pathways. The results highlight emerging opportunities to apply metabolic engineering to specific C1 pathways to improve pathway performance. Since the C1 landscape is dynamic, with new discoveries in the biochemistry of native pathways and new synthetic alternatives rapidly emerging, we present detailed procedures for these yield calculations to enable others to easily adapt them to additional scenarios as a foundation for establishing industrially relevant production strains.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103310"},"PeriodicalIF":7.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906357","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":"Editorial overview: Phosphate Special Issue","authors":"Chris Pratt , Lars M Blank","doi":"10.1016/j.copbio.2025.103309","DOIUrl":"10.1016/j.copbio.2025.103309","url":null,"abstract":"","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103309"},"PeriodicalIF":7.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906358","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}
Isabel Pardo , Maria T Manoli , Susana Capel , Alba Calonge-García , M Auxiliadora Prieto
{"title":"Enzymatic recycling and microbial upcycling for a circular plastics bioeconomy","authors":"Isabel Pardo , Maria T Manoli , Susana Capel , Alba Calonge-García , M Auxiliadora Prieto","doi":"10.1016/j.copbio.2025.103307","DOIUrl":"10.1016/j.copbio.2025.103307","url":null,"abstract":"<div><div>Since the 1950s, plastics have become commodity materials that are present in virtually every aspect of our daily lives. However, the current economic model of plastics is fundamentally linear, with less than 10% of plastics returning to the value chain at their end of life. In recent years, efforts have been dedicated to develop new technologies that can change this model to a circular economy for plastics, including enzymatic recycling and biological upcycling to value-added products. Here, we will review recent advances made in this rapidly evolving field and discuss how further development of these technologies could contribute to reduce the share of postconsumer plastic waste that is diverted toward landfilling and incineration.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103307"},"PeriodicalIF":7.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891963","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":"Optimizing Cupriavidus necator H16 as a host for aerobic C1 conversion","authors":"Stefano Donati , Christopher W Johnson","doi":"10.1016/j.copbio.2025.103306","DOIUrl":"10.1016/j.copbio.2025.103306","url":null,"abstract":"<div><div>Biological systems capable of converting CO<sub>2</sub> or CO<sub>2</sub>-derived, single-carbon (C1) compounds can be used to reduce or reverse carbon emissions while establishing a circular bioeconomy to provide sustainable sources of the fuels, foods, and materials humanity relies on. A robust bioeconomy will rely upon a variety of microorganisms capable of assimilating C1 compounds and converting them to valuable products at industrial scale. While anaerobic microbes are ideal hosts for production of short-chain acids and alcohols, microbes capable of aerobic respiration are well suited for biosynthesis of higher molecular weight products. One such organism is the gram-negative soil bacterium <em>Cupriavidus necator</em>, which has been utilized in commercial production of biopolymers for decades. More recently, its capability of robust, aerobic growth on CO<sub>2</sub> has inspired research efforts that have advanced it toward becoming one of the leading bacterial hosts for C1-based biomanufacturing. This review highlights those efforts in the context of the characteristics that have historically made <em>C. necator</em> an excellent host for industrial bioconversion processes: its metabolic versatility, ability to grow rapidly to high cell densities, and genetic amenability.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103306"},"PeriodicalIF":7.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868793","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}
Henri Ingelman , James K Heffernan , Kaspar Valgepea
{"title":"Adaptive laboratory evolution for improving acetogen gas fermentation","authors":"Henri Ingelman , James K Heffernan , Kaspar Valgepea","doi":"10.1016/j.copbio.2025.103305","DOIUrl":"10.1016/j.copbio.2025.103305","url":null,"abstract":"<div><div>Gas fermentation using acetogens can help humankind transition from petroleum-based industries to more sustainable alternatives. Acetogens are a unique set of organisms that efficiently convert carbon oxide waste gases into chemicals, such as ethanol and acetate. While acetogens are already used in commercially operated bioprocess facilities, the field is still affected by challenging genetic manipulation workflows and a developing knowledge of acetogen metabolism. Adaptive laboratory evolution (ALE) can uniquely contribute here, through evolution of organisms guided by synthetically created niches, which delivers strains with industrially relevant phenotypes and helps to resolve genotype–phenotype relationships. Here, we review the expanding use of ALE for acetogens, showcasing results regarding fundamental understanding of acetogens and improvement of phenotypes — faster growth/substrate utilisation, elimination of media components, improving stress tolerance, and improving growth and robustness in bioreactor cultures. These works provide the field with opportunities to further engineer and manipulate acetogen traits for industrial bioprocesses and improve the understanding of genotype–phenotype relationships.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103305"},"PeriodicalIF":7.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859393","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}
Ezequiel Santillan , Soheil A Neshat , Stefan Wuertz
{"title":"Disturbance and stability dynamics in microbial communities for environmental biotechnology applications","authors":"Ezequiel Santillan , Soheil A Neshat , Stefan Wuertz","doi":"10.1016/j.copbio.2025.103304","DOIUrl":"10.1016/j.copbio.2025.103304","url":null,"abstract":"<div><div>Microbial communities are corner stones of environmental biotechnology, driving essential processes such as waste degradation, pollutant removal, and nutrient cycling, all fundamental to industrial bioprocesses and sustainability. The structure and functions of these communities are influenced by environmental disturbances, which can arise from changes in operational conditions. Understanding disturbance–stability dynamics, including the roles of rare taxa and gene potential, is crucial for optimizing processes such as wastewater treatment, bioenergy production, and environmental bioremediation. This review highlights recent theoretical, technical, and experimental advances — including ecological theory, multiscale approaches, and the use of machine learning and artificial intelligence — to predict community responses to disturbances. Together, these insights offer a valuable outlook for developing scalable and robust biotechnology applications.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"93 ","pages":"Article 103304"},"PeriodicalIF":7.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839095","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}