Trends in biotechnologyPub Date : 2026-10-01Epub Date: 2026-07-27DOI: 10.1016/j.tibtech.2026.07.009
Wilson Wen Bin Goh, Cheng Chang, Hui Peng, Linhai Xie, Fuchu He
{"title":"Driving the future of proteome-based innovations: the π-HuB project.","authors":"Wilson Wen Bin Goh, Cheng Chang, Hui Peng, Linhai Xie, Fuchu He","doi":"10.1016/j.tibtech.2026.07.009","DOIUrl":"10.1016/j.tibtech.2026.07.009","url":null,"abstract":"<p><p>π-HuB is an international consortium that aims to reframe proteomics from a catalog of proteins into a navigator of biological transitions. By integrating proteomic data, AI, standards, governance, and international infrastructure, it could accelerate discovery and clinical actionability while ensuring that large-scale proteomics becomes scalable, interpretable, ethical, and globally impactful.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2813-2816"},"PeriodicalIF":16.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in biotechnologyPub Date : 2026-10-01Epub Date: 2026-04-23DOI: 10.1016/j.tibtech.2026.03.026
Xiongwen Li, Zhetao Guo, Yi Li, Zhu Liang, Ziyi Liu, Ke Wu, Jiahao Luo, Yuesheng Zhang, Lizheng Liu, Manda Sun, Yuanyuan Huang, Yu Chen, Tao Yu, Jens Nielsen, Hongting Tang, Feiran Li
{"title":"Leveraging large language models for metabolic engineering design.","authors":"Xiongwen Li, Zhetao Guo, Yi Li, Zhu Liang, Ziyi Liu, Ke Wu, Jiahao Luo, Yuesheng Zhang, Lizheng Liu, Manda Sun, Yuanyuan Huang, Yu Chen, Tao Yu, Jens Nielsen, Hongting Tang, Feiran Li","doi":"10.1016/j.tibtech.2026.03.026","DOIUrl":"10.1016/j.tibtech.2026.03.026","url":null,"abstract":"<p><p>Establishing efficient cell factories involves a continuous process of trial and error due to metabolic complexity. This complexity makes predicting effective engineering targets a challenging task. Therefore, successful previous designs are vital for future cell factory development. In this study, we developed a method using large language models to extract metabolic engineering strategies from research articles. We created a database containing over 29 006 metabolic engineering entries, 1210 products, and 751 organisms. Using this database, we trained a deep learning model to predict engineering targets for cell factories. Our model outperformed traditional algorithms, demonstrated strong generalization to unseen products and multigene combinations, and was experimentally validated with geraniol overproduction in yeast, leading to the identification of several novel targets. Our study provides a valuable dataset, a chatbot, and an engineering target prediction model for the metabolic engineering field and exemplifies an efficient method for leveraging existing knowledge for future predictions.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"3104-3125"},"PeriodicalIF":16.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrated directed evolution and semirational design of Pyrococcus furiosus Argonaute for ultrasensitive tetracycline detection.","authors":"Yanyan Chai, Bosheng Zhou, Wanqi Chen, Yuxuan Hu, Bingjie Zheng, Guozhen Liu, Yonggang Hu","doi":"10.1016/j.tibtech.2026.04.008","DOIUrl":"10.1016/j.tibtech.2026.04.008","url":null,"abstract":"<p><p>In this study, we report an integrated strategy combining directed evolution and semirational design to engineer a high-performance Pyrococcus furiosus Argonaute (PfAgo) variant. The optimized variant exhibited an 8.85-fold increase in catalytic efficiency, substantially enhanced soluble expression, and improved tolerance to elevated salt and metal ion conditions, enabling sensitive nucleic acid detection with a detection limit in the picomolar range. Mechanistic analyses suggested that these improvements may arise from reinforcement of the dimerization interface to stabilize the enzyme's active state, optimization of the catalytic center, and the introduction of charge-shielding salt bridges. Finally, a biosensing platform based on the engineered PfAgo achieved a detection limit of 10 fmol l<sup>-1</sup> for tetracycline, demonstrating its strong potential for sensitive and robust detection. This work provides a generalizable framework for enhancing Argonaute performance and advances their application in field-deployable diagnostics across clinical, environmental, and food safety settings.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"3054-3079"},"PeriodicalIF":16.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic engineering of Saccharomyces cerevisiae for the biosynthesis of indole-derived compounds.","authors":"Mengchu Sun, Xiaolin Shen, Xinxiao Sun, Jia Wang, Qipeng Yuan","doi":"10.1016/j.tibtech.2026.09.006","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.09.006","url":null,"abstract":"<p><p>Indole-3-acetonitrile (IAN) and its derivatives-indole-3-carboxaldehyde (I3A), indole-3-carboxylic acid (I3CA), and 3,3'-diindolylmethane (DIM)-are high-value indole-derived compounds widely used in the chemical, pharmaceutical, and nutraceutical industries. However, their de novo microbial production has not yet been achieved. In this study, we constructed a Saccharomyces cerevisiae platform for the de novo biosynthesis of IAN and its downstream derivatives. Reconstruction and optimization of the native plant pathway enabled production of 189.02 mg/l IAN from glucose, and the pathway was subsequently extended to I3A and I3CA, reaching titers of 65.85 and 13.95 mg/l, respectively. Furthermore, an artificial biosynthetic route to DIM was constructed by identifying a previously uncharacterized I3A reductase, enabling the microbial production of DIM from glucose. This work establishes a microbial platform for de novo biosynthesis of IAN and its derivatives and demonstrates a general strategy for producing natural and nonnatural indole derivatives.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unnatural amino acids program thermoresponsive protein-polymer diblocks into shape-shifting nanostructures.","authors":"Daniela S Strugach, Yuval Pasternak, Oren Tiv, Federico Kaufman, Itzhak Levi, Miriam Amiram","doi":"10.1016/j.tibtech.2026.09.008","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.09.008","url":null,"abstract":"<p><p>Control over the morphology and function of self-assembling polymers remains a central challenge in engineering adaptive biomaterials and synthetic biological systems. Here, we establish that recombinant elastin-like polypeptide-resilin-like polypeptide diblocks can be programmed through incorporation of unnatural amino acids (uAAs) to undergo multistep, temperature-dependent phase transitions that generate shape-shifting nanostructures, including micelles, vesicles, and higher-order assemblies not typically accessible in conventional protein materials, thereby expanding their structural and functional design space. Incorporation of only six uAAs (<1.5% of residues) is sufficient to program phase behavior and assembly pathways, with uAA hydrophobicity and sequence position governing morphology and structural transitions. Photo-switchable uAAs further enable reversible, light-driven control over nanostructure morphology, modulating substrate encapsulation and enzymatic activity. Together, these findings define a genetically encoded design framework for adaptive protein materials and expand opportunities for their use in biotechnology, including synthetic organelle-like systems, dynamic biomolecular assemblies, responsive biocatalysis, and drug delivery.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongdan Wang, Saeyoung Kim, Zhen Qin, Zhao Wang, Seongkyu Yoon
{"title":"Advancing mRNA therapeutics from design to delivery.","authors":"Yongdan Wang, Saeyoung Kim, Zhen Qin, Zhao Wang, Seongkyu Yoon","doi":"10.1016/j.tibtech.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.09.005","url":null,"abstract":"<p><p>mRNA therapeutics have emerged as a transformative platform for vaccines and protein replacement therapies, yet their broader clinical and commercial translation remains constrained by challenges in product stability, safety, potency, and delivery efficiency. This review provides a comprehensive overview of the current state of mRNA therapeutic development across the entire product lifecycle, spanning RNA design, manufacturing process optimization and characterization, scale-up and continuous manufacturing, lipid nanoparticle design, formulation, and delivery. Unlike prior reviews that focus on individual stages, we present an end-to-end perspective linking drug substance and drug product development, with emphasis on technological advances over the past 5 years. By integrating these advances, this review offers a practical roadmap for overcoming key bottlenecks and accelerating next-generation mRNA therapeutics.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Meng, Tobias Karmainski, Aziz Ben Ammar, Anka Sieberichs, Yannick Branson, Peer Vossen, Tobias Schwanemann, Hendrik Ballerstedt, Uwe T Bornscheuer, Ren Wei, Lars M Blank
{"title":"Engineering Pseudomonas putida KT2440 for open-loop upcycling of mixed plastics.","authors":"Hao Meng, Tobias Karmainski, Aziz Ben Ammar, Anka Sieberichs, Yannick Branson, Peer Vossen, Tobias Schwanemann, Hendrik Ballerstedt, Uwe T Bornscheuer, Ren Wei, Lars M Blank","doi":"10.1016/j.tibtech.2026.08.017","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.017","url":null,"abstract":"<p><p>Current recycling technologies address less than 10% of global plastic waste, necessitating alternative valorization routes. Biological upcycling via enzymatic depolymerization combined with microbial conversion of the resulting monomers offers a promising pathway to transform mixed-plastic waste into valuable alternatives. In this research article, we employed a single engineered Pseudomonas putida KT2440 for simultaneous co-utilization of five plastic monomers including ethylene glycol, terephthalate, adipate, 1,4-butanediol, and l-lactic acid, which can be derived from enzymatic hydrolysis of polyethylene terephthalate (PET), poly(butylene adipate-co-terephthalate) (PBAT), polyester polyurethanes (PUs), and polylactic acid. Continuous fermentation over 21 days with alternating mixed-monomer feeds achieved steady-state growth and complete substrate depletion, yielding adaptive mutations that informed iterative strain improvement. Further engineering enabled the biosynthesis of (R)-3-hydroxybutyrate (R-3HB), and 0.70 g l<sup>-1</sup> R-3HB was produced directly from enzymatic hydrolysates of blended PET, PBAT, and thermoplastic PU. These results establish a viable bio-based approach for upcycling realistic mixed plastics into value-added bioproducts.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suyeon Kim, Yu-Jin Kim, Jin Yoo, Jinkee Hong, Youngmee Jung
{"title":"Nanozymes and the restoration of immune tolerance in autoimmune diseases.","authors":"Suyeon Kim, Yu-Jin Kim, Jin Yoo, Jinkee Hong, Youngmee Jung","doi":"10.1016/j.tibtech.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.09.002","url":null,"abstract":"<p><p>Autoimmune diseases (ADs) are characterized by persistent immune dysregulation and oxidative imbalance, yet current therapies largely rely on broad immunosuppression that rarely restores durable immune homeostasis. Growing evidence indicates that reactive oxygen species (ROS) function as both inflammatory mediators and essential immune regulators, limiting the effectiveness of indiscriminate ROS scavenging. Here, we highlight nanozymes as emerging catalytic therapeutics for (ADs) and redefine their role as regulators of redox-guided immune homeostasis. We propose a catalytic redox set-point framework in which nanozymes restore a physiological redox window that supports immune regulation while constraining pathological inflammation. This perspective establishes a unifying mechanistic link between nanozyme catalysis and immune restoration, and outlines future opportunities for tolerance-oriented design and clinical translation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasmid copy number control offers a versatile tool in synthetic biology applications.","authors":"Chentao Yong, Andrés Felipe Carrillo Rincón, Shivang Hina-Nilesh Joshi, Rumail Memon, Andras Gyorgy","doi":"10.1016/j.tibtech.2026.07.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.005","url":null,"abstract":"<p><p>Plasmids are typically regarded as static delivery vehicles for foreign DNA. Here, we expose the pivotal role that plasmid copy number (PCN) control can play in synthetic biology, not only in Escherichia coli but also in the next-generation bacterial workhorse Vibrio natriegens. We show that the antibiotic selection marker can impact PCN, thus affecting growth and protein production, and that cells can be cotransformed with multiple variants of the same plasmid, with their PCN controlled simultaneously and in unison. We reveal that plasmid loss can be mitigated via the integration of an additional origin of replication (ori) and that PCN control can be leveraged to modulate horizontal gene transfer, which we illustrate within the context of conjugation-based intercellular communication. Finally, we expand the MoClo modular cloning framework with inducible PCN control for rapid prototyping and to enhance the performance of complex biocircuits.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}