{"title":"Emerging strategies to develop novel genetically encoded biosensors.","authors":"Lili Chang, Jin Wang, Meng Wang, Yue Zhang","doi":"10.1016/j.tibtech.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.014","url":null,"abstract":"<p><p>The current biosensor inventory is inadequate for the multitude of metabolites and proteins needing detection. Assisted by new technologies and research paradigms such as multi-omics analysis and de novo protein design, emerging strategies provide a promising avenue for the development of novel, tailored genetically encoded biosensors for various applications.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086697","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":"CRISPR-based non-nucleic acid detection.","authors":"Shanshan Zhang, Dayong Xu, Feng Li, Jin Wang","doi":"10.1016/j.tibtech.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.012","url":null,"abstract":"<p><p>Characterization of clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) trans-cleavage activities has initiated the era of next-generation CRISPR diagnostics. By using the trans-cleavage reaction for signal output, CRISPR systems have been engineered to detect non-nucleic acids (NNAs), including ions, inorganic small molecules, organic compounds, proteins, and bacteria. Diverse strategies are being used to specifically recognize NNAs and regulate Cas trans-cleavage activities, via generation or depletion of output signals. In this review, we introduce the principles and advantages of CRISPR-based NNA detection. We then classify CRISPR-based NNA detection strategies into three classes: the generation or depletion of free activators, synthesis of crRNAs, and reconstruction of active Cas effectors. Finally, we discuss the challenges and potential strategies to advance both clinical and nonclinical applications of CRISPR-based NNA detection.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080652","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}
Linda van Oosten, Jort J Altenburg, Gwen Nowee, Dennis Kenbeek, Tessa Neef, Thomas Rouw, Vivian I P Tegelbeckers, Jans van der Heijden, Saskia Mentink, Wessel Willemsen, Christina S Hausjell, Louis Kuijpers, Leo van der Pol, António Roldão, Ricardo Correia, Erwin van den Born, René H Wijffels, Dirk E Martens, Monique M van Oers, Gorben P Pijlman
{"title":"Engineered thermoswitch in the baculovirus expression vector system for production of virus-like particle vaccines with minimized baculovirus contaminants.","authors":"Linda van Oosten, Jort J Altenburg, Gwen Nowee, Dennis Kenbeek, Tessa Neef, Thomas Rouw, Vivian I P Tegelbeckers, Jans van der Heijden, Saskia Mentink, Wessel Willemsen, Christina S Hausjell, Louis Kuijpers, Leo van der Pol, António Roldão, Ricardo Correia, Erwin van den Born, René H Wijffels, Dirk E Martens, Monique M van Oers, Gorben P Pijlman","doi":"10.1016/j.tibtech.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.004","url":null,"abstract":"<p><p>The baculovirus expression vector system (BEVS) is commercially used for producing recombinant (glyco)proteins, gene therapy vectors, and virus-like particles (VLPs) in insect cells. A major challenge in VLP downstream processing (DSP) is the removal of similarly sized baculovirus particle contaminants. Herein we engineered a genetic ON/OFF thermoswitch in the baculovirus vector by mutating the essential gp41 gene. This temperature-sensitive (ts) baculovirus expression system (BacFree<sup>ts</sup>) produces high baculovirus titers at 27°C, while contaminating baculovirus production switches off at elevated temperatures. We demonstrate scalable VLP production for chikungunya virus (CHIKV), West Nile virus (WNV), coxsackievirus A6, and foot-and-mouth disease virus (FMDV) at 33°C, concomitant with baculovirus particle reduction up to 99.97%. However, elevated temperature moderately affected the yield of two out of four VLP designs. BacFree<sup>ts</sup> is compatible with commonly used insect cells and scalable infection strategies. BacFree<sup>ts</sup> effectively reduces baculovirus contaminants in the upstream VLP production phase, which will facilitate DSP of human and veterinary VLP-based vaccines.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055206","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}
Dong Yin, Qingxiao Pang, Yingbo Yuan, Tianyuan Su, Mengmeng Liu, Qian Wang, Jin Hou, Qingsheng Qi
{"title":"An in vivo target mutagenesis system for multiple hosts.","authors":"Dong Yin, Qingxiao Pang, Yingbo Yuan, Tianyuan Su, Mengmeng Liu, Qian Wang, Jin Hou, Qingsheng Qi","doi":"10.1016/j.tibtech.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.005","url":null,"abstract":"<p><p>In vivo target mutagenesis is a powerful approach to accelerate protein evolution. However, current approaches have been primarily developed in conventional organisms, limiting their capacity to evolve proteins with subtle variations across non-conventional host species. Here, we design an in vivo target mutagenesis system for multiple hosts (ITMU) utilizing the broad host-range plasmid RSF1010 replication element. The ITMU, which is based on a deaminase-helicase fusion and a primase error-prone DNA polymerase I fusion, induces all types of mutation in the target plasmid harboring the RSF1010 replicon, at a mutation rate 1.18 × 10<sup>5</sup>-fold higher than that of the host genome. We show that ITMU-based in vivo continuous evolution is effective in Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, and Yarrowia lipolytica. This demonstrates that the ITMU is applicable to multiple microbial chassis and provides a viable alternative to in vivo continuous evolution systems.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034111","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}
Chantal Treinen, Christina Peternell, Philipp Noll, Olivia Magosch, Rudolf Hausmann, Marius Henkel
{"title":"Molecular process control for industrial biotechnology.","authors":"Chantal Treinen, Christina Peternell, Philipp Noll, Olivia Magosch, Rudolf Hausmann, Marius Henkel","doi":"10.1016/j.tibtech.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.003","url":null,"abstract":"<p><p>The development of sustainable and economically competitive biotechnological processes is a central challenge of modern industrial biotechnology. Conventional strategies such as macroscopic and molecular bioprocess design are often insufficient to exploit their full potential. To circumvent this, molecular process control provides the missing link to further consolidate various optimization strategies to achieve multilayered process design. This review highlights the molecular mechanisms that can be exploited for molecular process control. These can either be endogenous or specifically implemented into the organism, and comprise regulatory mechanisms at the transcriptional, translational, and system levels. In addition to serving as a design tool to enhance existing bioprocesses, molecular process control is the gateway to biotechnological advances that will extend the boundaries of future process design.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050232","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":"Intelligent biomanufacturing of water-soluble vitamins.","authors":"Fuqiang Song, Heng Zhang, Zhijie Qin, Jingwen Zhou","doi":"10.1016/j.tibtech.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.04.007","url":null,"abstract":"<p><p>Given the crucial role of water-soluble vitamins in the human body and the rising demand for natural sources, their biosynthesis has gained the attention of researchers. This review offers a comprehensive look at recent progress in water-soluble vitamin biosynthesis, emphasizing synthetic biotechnology for green biomanufacturing. Specifically, it encompasses the optimization of biological components, pathways, and systems, as well as energy metabolism regulation, stress-tolerance enhancement, high-throughput screening, and the upscaling of production processes. It also envisages intelligent biomanufacturing platforms, highlighting the role of systems biology and artificial intelligence (AI), and proposes future research directions, such as integrating AI-driven metabolic models, enzyme engineering, and cell-free systems, to address limitations in the efficiency, toxicity, and scalability of water-soluble vitamin production.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046849","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}
Samapti Kundu, Simone Potenti, Zachary A Quinlan, Helena Willard, Justin Chen, Timothy Noritake, Natalie Levy, Zahra Karimi, Hendrikje Jorissen, Joshua R Hancock, Crawford Drury, Linda Wegley Kelly, Luisa De Cola, Shaochen Chen, Daniel Wangpraseurt
{"title":"Biomimetic chemical microhabitats enhance coral settlement.","authors":"Samapti Kundu, Simone Potenti, Zachary A Quinlan, Helena Willard, Justin Chen, Timothy Noritake, Natalie Levy, Zahra Karimi, Hendrikje Jorissen, Joshua R Hancock, Crawford Drury, Linda Wegley Kelly, Luisa De Cola, Shaochen Chen, Daniel Wangpraseurt","doi":"10.1016/j.tibtech.2025.03.019","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.03.019","url":null,"abstract":"<p><p>Anthropogenic stressors pose substantial threats to the existence of coral reefs. Achieving successful coral recruitment stands as a bottleneck in reef restoration and hybrid reef engineering efforts. Here, we enhance coral settlement through the development of biomimetic microhabitats that replicate the chemical landscape of healthy reefs. We engineered a soft biomaterial, SNAP-X, comprising silica nanoparticles (NPs), biopolymers, and algal exometabolites, to enrich reef microhabitats with bioactive molecules from crustose coralline algae (CCA). Coral settlement was enhanced over 20-fold using SNAP-X-coated substrates compared with uncoated controls. SNAP-X is designed to release chemical signals slowly (>1 month) under natural seawater conditions, and can be rapidly applied to natural reef substrates via photopolymerization, facilitating the light-assisted 3D printing of microengineered habitats. We anticipate that these biomimetic chemical microhabitats will be widely used to augment coral settlement on degraded reefs and to support ecosystem processes on hybrid reefs.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080645","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 : 2025-05-01Epub Date: 2024-09-27DOI: 10.1016/j.tibtech.2024.09.009
Fei Yu, Yongjin J Zhou
{"title":"Sustainable production of porphyrins through synthetic biology.","authors":"Fei Yu, Yongjin J Zhou","doi":"10.1016/j.tibtech.2024.09.009","DOIUrl":"10.1016/j.tibtech.2024.09.009","url":null,"abstract":"<p><p>Porphyrin compounds are versatile heterocyclic molecules with diverse applications. However, their high-level production is limited by strict biosynthetic regulation and low catalytic efficiency of pathway enzymes. This forum article focuses on recent breakthroughs in porphyrin biosynthesis across various species, aiming to promote the sustainable production of porphyrins through synthetic biology.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"996-999"},"PeriodicalIF":14.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354604","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":"Engineered, environmentally friendly leather-like bio-based materials.","authors":"Xinhua Liu, Xiaoyu Zhang, Xuechuan Wang, Ouyang Yue, Huie Jiang","doi":"10.1016/j.tibtech.2024.11.006","DOIUrl":"10.1016/j.tibtech.2024.11.006","url":null,"abstract":"<p><p>Leather is important to the global manufacturing industry, contributing to both the economy and society. However, because of ecological and ethical considerations, alternative bio-based materials to natural leather are now being investigated. Advancements in biotechnology and bio-based materials, combined with flourishing biomanufacturing, have driven product development. In recent years, animal-free, biotechnology-based leather-like material has seen significant growth. Recent progress in leather-like bio-based materials development has been achieved using proteins, mycelium, cellulose, and other sustainable natural materials. This review provides a comprehensive overview of these bio-based materials, addressing their challenges, practical implications, and potential to play a growing role in the emerging field of animal-free alternative. The development of 'future leather' has significant economic and environmental potential.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"1104-1115"},"PeriodicalIF":14.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772628","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 : 2025-05-01Epub Date: 2024-11-09DOI: 10.1016/j.tibtech.2024.10.002
Eylul Gulsen Yilmaz, Nedim Hacıosmanoğlu, Sebastian Bruno Ulrich Jordi, Bahtiyar Yilmaz, Fatih Inci
{"title":"Revolutionizing IBD research with on-chip models of disease modeling and drug screening.","authors":"Eylul Gulsen Yilmaz, Nedim Hacıosmanoğlu, Sebastian Bruno Ulrich Jordi, Bahtiyar Yilmaz, Fatih Inci","doi":"10.1016/j.tibtech.2024.10.002","DOIUrl":"10.1016/j.tibtech.2024.10.002","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) comprises chronic inflammatory conditions with complex mechanisms and diverse manifestations, posing significant clinical challenges. Traditional animal models and ethical concerns in human studies necessitate innovative approaches. This review provides an overview of human intestinal architecture in health and inflammation, emphasizing the role of microfluidics and on-chip technologies in IBD research. These technologies allow precise manipulation of cellular and microbial interactions in a physiologically relevant context, simulating the intestinal ecosystem microscopically. By integrating cellular components and replicating 3D tissue architecture, they offer promising models for studying host-microbe interactions, wound healing, and therapeutic approaches. Continuous refinement of these technologies promises to advance IBD understanding and therapy development, inspiring further innovation and cross-disciplinary collaboration.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"1062-1078"},"PeriodicalIF":14.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629164","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}