Javier Vicente, Santiago Benito, Domingo Marquina, Antonio Santos
{"title":"Microbial tools and regulatory innovations for climate-resilient winemaking.","authors":"Javier Vicente, Santiago Benito, Domingo Marquina, Antonio Santos","doi":"10.1016/j.tibtech.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.001","url":null,"abstract":"<p><p>Climate-induced acidity loss threatens wine quality, prompting sustainable microbial acidification strategies using Lachancea thermotolerans. This yeast naturally reduces pH and ethanol, aligns with consumer preferences, and benefits from omics-driven selection and enabling policy frameworks. Adaptation requires coordinated biotechnological innovation, institutional backing, and clear consumer communication to maintain sustainability and competitiveness.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092540","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":"Nanobotic microbiomes against emerging vascular pathogens in agriculture.","authors":"Ayesha Ahmed, Yongmei Li, Yueqiu He, Dake Zhao, Shahzad Munir, Rajender S Varma","doi":"10.1016/j.tibtech.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.015","url":null,"abstract":"<p><p>Vascular diseases in plants are exceptionally difficult to control. Escalating global climate change further increases the risks of outbreaks from existing and emerging pathogens. Nano-enabled microbiome engineering (NME) represents an innovative framework for targeted vascular plant pathogen control, offering a sustainable platform to enhance agricultural resilience and productivity.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092527","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}
Georgii Emelianov, Dong-Uk Song, Aporva Kamath, Hyeongseop Kim, Geunyeong Lee, Ha-Neul Kim, Kil Koang Kwon, Bong Hyun Sung, Dae-Hee Lee, Nathan J Hillson, Haseong Kim, Sanguk Kim, Hyewon Lee, Seung-Goo Lee
{"title":"Semi-automated biofoundry workflows for sequence coevolution-guided isoprene synthase engineering.","authors":"Georgii Emelianov, Dong-Uk Song, Aporva Kamath, Hyeongseop Kim, Geunyeong Lee, Ha-Neul Kim, Kil Koang Kwon, Bong Hyun Sung, Dae-Hee Lee, Nathan J Hillson, Haseong Kim, Sanguk Kim, Hyewon Lee, Seung-Goo Lee","doi":"10.1016/j.tibtech.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.007","url":null,"abstract":"<p><p>Biofoundries serve as transformative platforms for accelerating the engineering of enzymes and microorganisms toward biomanufacturing. In this study, we developed scalable enzyme engineering workflows tailored for biofoundry applications, focusing on isoprene synthase (IspS) - a critical rate-limiting enzyme in the isoprene biosynthesis. By integrating computational mutation design based on sequence coevolution analysis and laboratory automation, we conducted three rounds of site-directed mutagenesis and screening. Approximately 100 genetic mutants were synthesized per round and these workflows can be easily scaled up to thousands without extensive optimization. Moreover, this approach enabled the rapid identification of IspS variants with up to 4.5-fold improvement in catalytic efficiency and simultaneously enhanced thermostability. Additionally, introducing the engineered IspS into Methylococcus capsulatus Bath improved methane-to-isoprene bioconversion, achieving a titer of 319.6 mg/l. These scalable workflows establish a robust framework for enzyme engineering within biofoundries. This provides a basis for the development of innovative biotechnological advancements.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058690","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}
Fuqiang Song, Heng Zhang, Ke Wang, Kun Qiu, Shike Liu, Xinran Yin, Changtai Zhang, Jingwen Zhou
{"title":"In vivo continuous evolution via phenotypic sorting to alleviate metabolic bottlenecks in β-alanine production.","authors":"Fuqiang Song, Heng Zhang, Ke Wang, Kun Qiu, Shike Liu, Xinran Yin, Changtai Zhang, Jingwen Zhou","doi":"10.1016/j.tibtech.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.008","url":null,"abstract":"<p><p>β-Alanine is an important platform chemical whose biosynthesis efficiency is limited by pathway bottlenecks and enzyme constraints. In this study, to overcome genetic interactions for β-alanine production, we systematically engineered Escherichia coli MG1655 through modular pathway optimization and combinatorial regulation. To overcome the limitations of L-aspartate-α-decarboxylase from Bacillus subtilis (PanD<sub>bsu</sub>), we developed an in vivo evolution platform combining base-editing systems with biosensor guidance, thus generating PanD<sub>bsu</sub> variants with enhanced activity. This system facilitated high-throughput screening and real-time monitoring of β-alanine production and accelerated mutant selection. Furthermore, site saturation and iterative mutations identified a beneficial PanD<sub>bsu</sub><sup>T4E</sup> mutant, which enhanced specific β-alanine production in engineered strain MA31 by 62.45%. Structural and functional analysis revealed that PanD<sub>bsu</sub><sup>T4E</sup> stabilized its quaternary structure via a Glu-Lys salt bridge. This work describes a scalable strategy for addressing pathway bottlenecks and highlighted the potential of integrating protein engineering with biosensor-guided evolution to optimize microbial cell factories.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055904","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}
Jing Chen, Rong Zhang, Xun Zhang, Chengjin Li, Jie Yang, Xiangbo Kong, Fu Liu, Jiaxing Fang, Sufang Zhang
{"title":"Sustainable protection of multiple hosts against polyphagous pests using Plant Probiotic-Based Gene Silencing.","authors":"Jing Chen, Rong Zhang, Xun Zhang, Chengjin Li, Jie Yang, Xiangbo Kong, Fu Liu, Jiaxing Fang, Sufang Zhang","doi":"10.1016/j.tibtech.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.004","url":null,"abstract":"<p><p>RNAi is a gene-silencing mechanism mediated by double-stranded RNA (dsRNA) molecules and is a promising pest control technology. However, challenges, such as limited persistence or narrow plant protection spectra in current RNAi application strategies, hinder its effectiveness against polyphagous pests. Here, we report an approach using plant probiotics to express dsRNA, propelling sustainable protection of multiple host plants. A Bacillus strain isolated from host plants of the polyphagous pest Hyphantria cunea, was engineered to express dsRNA targeting the pest. The modified SH-F8 strain significantly reduced H. cunea pupation rates and increased mortality by disrupting both energy metabolism and cuticle formation. The engineered SH-F8 strain exhibited successful colonization in two host plant species of H. cunea under field conditions, with enhanced population densities appearing under high-temperature/high-humidity conditions. This approach, termed 'Plant Probiotic-Based Gene Silencing' (PPGS), may offer a sustainable solution for multi-plant protection against polyphagous pests.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041344","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}
Federico Germani, Julian W März, Alessandro Luciani, Olivier Devuyst, Nikola Biller-Andorno
{"title":"Ethical and legal considerations of digital animal models: pioneering reduction and replacement.","authors":"Federico Germani, Julian W März, Alessandro Luciani, Olivier Devuyst, Nikola Biller-Andorno","doi":"10.1016/j.tibtech.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.011","url":null,"abstract":"<p><p>The development of digital animal models represents a promising avenue for advancing the ethical principles of reduction and replacement in biomedical research. This paper discusses the potential of models built upon artificial intelligence (AI)-generated synthetic datasets simulating the characteristics and behaviors of model organisms, reducing reliance on live animals in research.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041383","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}
Margarita Bernal-Cabas, Karan Kumar, Owen Terpstra, Samira van den Bogaard, Aziz B Ammar, Susanna Mäkinen, Lukas Herwig, Marta de Almeida, Petri Tervasmäki, Lars M Blank, Tobias B Alter, Sonja Billerbeck
{"title":"Food production from air: gas precision fermentation with hydrogen-oxidising bacteria.","authors":"Margarita Bernal-Cabas, Karan Kumar, Owen Terpstra, Samira van den Bogaard, Aziz B Ammar, Susanna Mäkinen, Lukas Herwig, Marta de Almeida, Petri Tervasmäki, Lars M Blank, Tobias B Alter, Sonja Billerbeck","doi":"10.1016/j.tibtech.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.003","url":null,"abstract":"<p><p>The breach of six planetary boundaries highlights the need for sustainable food production. Aerobic hydrogen-oxidising bacteria (HOBs) convert atmospheric CO<sub>2</sub> and green hydrogen (H<sub>2</sub>) into biomass via gas fermentation, a process already used for food-grade single-cell protein production. This approach enables a supply chain independent of agriculture, requiring minimal land and water, with potential for carbon-neutral production and carbon capture. To expand beyond single-cell protein, HOBs must be engineered into cell factories for precision fermentation. Advances in synthetic biology, metabolic engineering, computational modelling, and bioreactor design have accelerated the development of scalable bioprocesses providing a blueprint for gas-based fermentation. We present a path forward using secreted recombinant milk protein as a case study, highlighting key challenges and opportunities.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034162","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}
An Lao, Weiqi Li, Yiting Sun, Yuting Cao, Yu Zhuang, Jianyong Wu, Dejian Li, Kaili Lin, Jing Mao, Jiaqiang Liu
{"title":"Metabolic and immunomodulatory control of type 2 diabetes via generating cellular itaconate reservoirs by inflammatory-targeting gene-therapy nanovesicles.","authors":"An Lao, Weiqi Li, Yiting Sun, Yuting Cao, Yu Zhuang, Jianyong Wu, Dejian Li, Kaili Lin, Jing Mao, Jiaqiang Liu","doi":"10.1016/j.tibtech.2025.07.025","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.025","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is characterized by persistent and unresolved tissue inflammation caused by the infiltration and dysregulation of immune cells. Current therapeutics targeting inflammatory immune cells for T2D remain limited. In this study, we analyzed single cell RNA from metabolic organs in T2D, revealing increased macrophage accumulation and a pathogenic macrophage subpopulation defined as NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3)<sup>+</sup> inflammatory and metabolically activated macrophages. To target these inflammatory cells, we developed nanovesicles encapsulating mitochondrial metabolic enzyme-related gene segments [immune-responsive gene 1 (IRG1)-overexpression plasmids] with cell membrane decoration. The nanovesicles functioned as cellular itaconate producers that elegantly circumvented the drug utilization barriers of a classic NLRP3 inhibitor and, as a mitochondria-reprograming system, mitigated fatty acid (FA)-associated metabolic dysfunction. The nanovesicles reversed inflammation, restored metabolic functions, and ameliorated obesity. Therefore, the metabolic and immunomodulatory functions of nanovesicles may offer translational opportunities for the prevention and treatment of T2D.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030607","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":"Flying seed-inspired sensors for remote environmental monitoring on Earth and beyond.","authors":"Sagar Arya, Lukáš Spíchal, Radek Zbořil","doi":"10.1016/j.tibtech.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.005","url":null,"abstract":"<p><p>Exploring mobility beyond traditional robotic systems such as walking, swimming, and jumping, flight through dispersal, gliding, or hovering remains an untapped frontier for advanced stimulus-responsive and -sensing materials. Nature-inspired engineering has been a foundational aspect of robotic innovations, and biohybrid and biomimetic flying seeds are now becoming a significant example of this concept. By mimicking the aerodynamic properties and dispersal mechanisms of natural seeds, semi- and fully artificial systems are being designed for environmental monitoring, precision agriculture, and disease management applications that require wide-area coverage. Scientists are biomimicking these structures to explore the Martian surface and subsurface. This opinion article highlights the potential of flying seed-inspired sensors to advance environmental monitoring on Earth and planets such as Mars and beyond.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016215","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}
Güniz Özer Bergman, Sonia Mecacci, Vitor A P Martins Dos Santos, Enrique Asin-Garcia
{"title":"Engineering chimeric signaling proteins for microbial whole-cell biosensors: from design to deployment.","authors":"Güniz Özer Bergman, Sonia Mecacci, Vitor A P Martins Dos Santos, Enrique Asin-Garcia","doi":"10.1016/j.tibtech.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.08.002","url":null,"abstract":"<p><p>Microbial whole-cell biosensors (MWCBs) harness living cells to detect analytes and produce measurable outputs, enabling continuous, low-cost, and in situ sensing. Central to MWCB function are modular sensing architectures, which can be reprogrammed to respond to diverse signals. Particularly, two-component systems (TCSs) and allosteric transcription factors (aTFs) offer modular, engineerable frameworks for building chimeric proteins. Recent advances in domain swapping, fusion point selection, and protein engineering are expanding the versatility and specificity of these systems, presenting new opportunities for tailored and multiplexed detection. However, translating chimeric MWCBs into real-world applications still faces multiple hurdles. This review examines current strategies for engineering TCS- and aTF-based biosensors and outlines key opportunities and challenges for their deployment in applications such as diagnostics, environmental monitoring, and biomanufacturing.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993655","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}