Trends in biotechnology最新文献

{"title":"Trehalose 6-phosphate as master switch for optimizing crop yield and resilience.","authors":"Muhammad Waqas, Chen Yaning, Yong-Ling Ruan, Zi-Ming Ren, Mark Stitt, Christoph-Martin Geilfus","doi":"10.1016/j.tibtech.2025.12.029","DOIUrl":"10.1016/j.tibtech.2025.12.029","url":null,"abstract":"<p><p>Crop breeding faces the challenge of balancing yield with resource efficiency and stress tolerance. The key regulatory metabolite trehalose 6-phosphate (T6P) integrates carbon status with growth and stress responses. Manipulating T6P levels through genetic modification or chemical intervention provides a powerful tool to tackle the growing challenges of crop production.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2506-2510"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258904","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":"Machine learning for designing low-risk microbial consortia pesticides.","authors":"Mónica Garcés-Ruiz, Belén Guijarro Díaz-Otero, Livio Antonielli, João Pedro Saraiva, Dimitrios Karpouzas, Stéphane Declerck","doi":"10.1016/j.tibtech.2025.12.027","DOIUrl":"10.1016/j.tibtech.2025.12.027","url":null,"abstract":"<p><p>Microbial consortia, considered low-risk pesticides (LRPs), appear to be valuable tools for reducing our dependence on chemical pesticides. However, their use is limited by inconsistent product efficacy and registration difficulties. Artificial intelligence (AI) and machine learning (ML) offer solutions for designing and evaluating synthetic microbial communities (SynComs), predicting their compatibility, ecological stability, and biocontrol efficacy. The transition from laboratory discovery of SynCom-based LRPs to field application and commercialization could be significantly accelerated. Here, we review the methods and steps necessary to establish reliable SynComs and describe how AI and ML approaches could improve the construction and validation of SynCom-based LRPs to obtain more specific results that can contribute to their risk assessment.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2596-2610"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481676","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":"A universal light-controlled highly sensitive one-pot CRISPR/Cas12a diagnostic based on structure-engineered crRNA.","authors":"Jieyu Cui, Lulu Zhang, Jing Zhou, Ting Shi, Shangyi Wu, Tenghui Dai, Lijun Hao, Junjie Pan, Xiaodan Lai, Wentao Lu, Xingxu Huang, Zhanjun Li, Liangxue Lai, Xinjie Wang","doi":"10.1016/j.tibtech.2026.03.018","DOIUrl":"10.1016/j.tibtech.2026.03.018","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR)-based nucleic acid detection has transformed molecular diagnostics through its speed and accuracy; however, one-pot formats are often limited by sensitivity and field suitability. Herein, we developed a universal light-controlled high-sensitivity one-pot CRISPR/Cas12a testing (ULTRAt) platform based on structure-engineered CRISPR RNA (crRNA) scaffolds. By incorporating photocaged 6-nitropiperonyloxymethyl groups into the crRNA stem-loop, Cas12a activity is transiently suppressed during isothermal amplification via structural modulation, enabling efficient target enrichment. Subsequent UV irradiation removes the protecting groups, restoring the native conformation and activating robust trans-cleavage. ULTRAt achieves a limit of detection of two copies of monkeypox virus per reaction with a 15-min time-to-result, representing a 100-fold sensitivity improvement over conventional assays. The platform further supports single-nucleotide polymorphism discrimination and human papillomavirus 16/18 genotyping. Analysis of 91 clinical samples demonstrates strong concordance between ULTRAt and reference qPCR and sequencing assays. Collectively, ULTRAt enables rapid, ultra-sensitive, and versatile one-pot detection, supporting near-patient diagnostics and genotyping.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2699-2721"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676988","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":"Paenibacillus polymyxa cell factories for production of polymyxins.","authors":"Cai-Yun Wu, Man-Man Xu, Jie Li, Tian-Qiong Shi","doi":"10.1016/j.tibtech.2025.12.021","DOIUrl":"10.1016/j.tibtech.2025.12.021","url":null,"abstract":"<p><p>Polymyxins synthesized by Paenibacillus polymyxa are critical for the treatment of multidrug-resistant infections, but production suffers from low yield and high cost. This forum article focuses on strategies for engineering P. polymyxa cell factories by optimizing genetic transformation systems, gene editing tools, and metabolic engineering strategies to enable sustainable polymyxin production.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2501-2505"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504766","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":"Advancements and challenges in CAR-NK cell therapy for cancer treatment.","authors":"Zhengshui Xu, Yu Li, Yundong Zhou, Changchun Ye, Junjie Kuang, Chengliang Yin, Danwen Zhao, Hui Guo, Narmatha Chellamani, Manimurugan Shanmuganathan, João Conde, Shiyuan Liu","doi":"10.1016/j.tibtech.2025.12.020","DOIUrl":"10.1016/j.tibtech.2025.12.020","url":null,"abstract":"<p><p>Chimeric antigen receptor natural killer (CAR-NK) cell therapy is an emerging cancer treatment offering advantages over CAR-T therapy, including reduced risks of cytokine release syndrome and graft-versus-host disease. This review highlights how genetic engineering enhances natural killer cells' innate tumor-killing abilities through CAR expression. Preclinical and clinical studies show promising antitumor responses, yet challenges remain, such as ensuring in vivo persistence, overcoming the immunosuppressive tumor microenvironment, and addressing manufacturing hurdles. Strategies such as cytokine support, combination therapies, and novel CAR designs are explored to improve efficacy. Future directions include personalized approaches, novel antigen targets, and artificial intelligence integration. CAR-NK therapy holds strong potential as a safe, scalable, and effective modality in cancer immunotherapy.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2511-2529"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214397","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":"Dynamic control of integrin signaling for cell manipulation via molecularly imprinted decoy receptor.","authors":"Fan Ding, Jingjing Xu, Yue Ma, Zhaoyang Yao, Jia Gao, Kangni Shang, Karsten Haupt, Guoqing Pan","doi":"10.1016/j.tibtech.2026.03.015","DOIUrl":"10.1016/j.tibtech.2026.03.015","url":null,"abstract":"<p><p>Integrin plays a crucial role in human immune system activation and stem cell differentiation through interactions with the extracellular matrix (ECM). Reversible modulation of integrin signaling has illuminated the road toward broad-spectrum disease treatment and tissue regeneration. In this regard, an integrin-like decoy receptor, termed molecularly imprinted polymer (MIP), was synthesized via solid-phase imprinting to target the Arg-Gly-Asp (RGD) sequence, an integrin-binding motif abundantly present in the ECM. The MIP, with temperature-dependent RGD affinity, enabled dynamic intervention in integrin signaling, thereby modulating integrin-RGD-mediated immune response and cell differentiation. The MIP could, on demand, orchestrate macrophage phenotypes to display proinflammatory or anti-inflammatory traits, potentially beneficial at the early stage of tissue injury. Furthermore, stem cell fates could be controlled by MIP, showing potential to prevent hyperplasia caused by excessive differentiation. The proof-of-concept studies demonstrate the feasibility of MIP-based decoy receptors in the dynamic control of integrin signals and cell evolution, showing promise in tissue repair and related diseases.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2796-2811"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676986","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 and enzyme engineering for steroid hormone biosynthesis.","authors":"Qihang Chen, Changtai Zhang, Song Liu, Weizhou Zeng, Jingwen Zhou","doi":"10.1016/j.tibtech.2025.12.012","DOIUrl":"10.1016/j.tibtech.2025.12.012","url":null,"abstract":"<p><p>Steroid hormones are key signaling molecules regulating growth, metabolism, reproduction, and stress adaptation and are widely used as essential pharmaceuticals. Traditional production from sterol feedstocks through multistep chemical or microbial transformations is limited by inefficiency and scalability. Recent advances in synthetic biotechnology enable de novo biosynthesis of steroid hormones from simple carbon sources in yeasts and fungi. This review highlights metabolic rewiring to increase flux, cytochrome P450 enzyme engineering for side-chain cleavage, and hydroxylation to overcome rate-limiting bottlenecks of steroid hormone biosynthesis. We also discuss strategies to redesign steroid-transport pathways to alleviate intracellular accumulation and improve membrane export. Looking ahead, we envision integrating metabolic, enzyme, and transport engineering to build a scalable, data-driven 'intelligent' platform for sustainable steroid hormone biomanufacturing.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2545-2562"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044091","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":"Label-free, single-cell-precise, and monomeric-unit-resolved monitoring of biopolymer fermentation by ramanomics.","authors":"Jia Zhang, Xu Liu, Zhihang Chen, Xuan Zhou, Mingying Li, Zengyan Sun, Teng Xu, Taoran Zheng, Xiaomeng Wang, Xinnan Cui, Jiajun Du, Gongchao Jing, Yanmei Zhang, Mingqin Xu, Bo Ma, Fuli Li, Huiying Luo, Bin Yao, Guo-Qiang Chen, Jian Xu","doi":"10.1016/j.tibtech.2026.03.017","DOIUrl":"10.1016/j.tibtech.2026.03.017","url":null,"abstract":"<p><p>Rapid yet high-information-content monitoring of cellular metabolism during fermentation is highly desirable for process optimization. While single-cell Raman spectroscopy can rapidly distinguish intracellular biopolymer classes, finer-resolution discrimination of monomeric units remains challenging. In this study, we demonstrated that the ramanome can classify polyhydroxyalkanoate (PHA)-producing Halomonas bluephagenesis cells that synthesize either polyhydroxybutyrate or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) with 99.75% accuracy and simultaneously quantify total intracellular PHA and its constituent monomeric units (3-hydroxybutyrate and 4-hydroxybutyrate) at the single-cell level (median absolute deviation <3.8%). Such information enabled timely, data-driven selection of the optimal harvest time and revealed precursor competition between nucleic acid and PHA biosynthesis. Moreover, when monitoring PHA production in an industrial-scale 5000 l-fermenter, our method achieved a 12-min turnaround time, representing a more than100-fold acceleration over gas chromatography. Furthermore, tests on protein production by Saccharomyces cerevisiae and on lipid synthesis in Rhodococcus opacus supported its versatility. Thus, ramanomics is a valuable approach for process control and strain evaluation in biomanufacturing.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2771-2795"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677040","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":"Rationally designed light-inducible RNA-releasing protein for translational regulation and optogenetic control of gene therapies.","authors":"Shichao Li, Ting Gao, Yinhao Wang, Qingjing He, Huiling Ma, Hui Ye, Yuqing Shen, Yukai Wang, Yujue Wang, Xiaoqing Li, Shaocong Fang, Qidi Chen, Qi Liu, Gangyu Sun, Huhu Xin, Jianzhuang Xue, Sicun Liu, Min Zhu, Wenqing Xu, Zhizhi Wang, Jiawei Shao, Mingqi Xie","doi":"10.1016/j.tibtech.2026.03.004","DOIUrl":"10.1016/j.tibtech.2026.03.004","url":null,"abstract":"<p><p>In this study, we describe a rationally designed light-inducible RNA-releasing protein (LIRP) capable of inhibiting mRNA translation in the dark while permitting gene expression upon exposure to blue or ambient light. This LIRP-dependent gene switch is compatible with various delivery routes of gene- and cell-based therapy, such as subcutaneous implantation of microencapsulated light-sensitive cells or expression in various light-accessible body sites using single adeno-associated virus (AAV) vectors. To exemplify a gene therapy approach that directly harnesses ambient light as a natural illumination source to induce therapeutic action, we show how intradermal delivery of AAV2 vectors carrying a LIRP-regulated gene switch controlling murine thymic stromal lymphopoietin expression was effective in enabling light-dependent prevention and treatment of diet-induced obesity. To describe another therapeutic scenario, we engineered AAV2 vectors for LIRP-dependent expression of Vascular endothelial growth factor (VEGF) inhibitors for the treatment of retinal neovascular diseases. Upon intravitreal delivery into mice suffering from wet macular degeneration, VEGF inhibitors were constantly produced when animals were exposed to daylight, but therapeutic actions could be flexibly interrupted either by exposure to dark environments or by administration of a selective blue light filter at any point in time. When compared to conventional treatment strategies based on constitutive VEGF inhibition over the course of 3 months, we show that a regulated gene therapy approach through LIRP-dependent optogenetics was advantageous in maintaining a normal retina thickness. This work not only provides a valuable addition to the optogenetic toolbox but also offers a perspective to translate light-dependent gene switches toward therapeutic usage.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2646-2678"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646654","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":"The cellular harvest: a symbiotic road map for food sovereignty.","authors":"Dexter Achu Mosoh, Wagner A Vendrame","doi":"10.1016/j.tibtech.2025.12.022","DOIUrl":"10.1016/j.tibtech.2025.12.022","url":null,"abstract":"<p><p>The 'predatory replacement' model in agriculture is untenable. We propose a symbiotic framework valorizing farmer-supplied agricultural waste side-streams to fuel bioengineered plant callus for decentralized high-value metabolite biosynthesis. Anchored in open-source governance and codesign, this approach shifts from displacement to innovation, reintegrating farmers to enhance sovereignty and resilience.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2493-2497"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207749","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}