Miranda J Wallace, Christina Kratschmer, Brandon Brazil, Ilham Matiker, Esse M Evbuomwan, Jerome Prusa, Jasmine Najari, Rehan Mehta, Ana Romani, Sophia Zhang, Jie Ning, Ryan A Hagenson, James Liao, Bin Wang, Beth A Helmink, Gautam Dantas
{"title":"A combinatorial construct library enables an expanded expression range of secreted therapeutic proteins by probiotic yeast.","authors":"Miranda J Wallace, Christina Kratschmer, Brandon Brazil, Ilham Matiker, Esse M Evbuomwan, Jerome Prusa, Jasmine Najari, Rehan Mehta, Ana Romani, Sophia Zhang, Jie Ning, Ryan A Hagenson, James Liao, Bin Wang, Beth A Helmink, Gautam Dantas","doi":"10.1016/j.tibtech.2026.08.012","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.012","url":null,"abstract":"<p><p>Orally administered engineered probiotics, including Saccharomyces cerevisiae var. boulardii (Sb), are of emerging interest as protein therapeutic delivery platforms to treat gastrointestinal diseases. Tools to readily optimize protein output are required to optimize the therapeutic index of Sb-produced therapies. In this study, a 125-plex Sb secretion construct library was developed consisting of all possible combinations of five promoters, five secretion signals, and five terminators, which enabled a greater than 1800-fold range in Sb expression of a Gaussia luciferase (GLuc) reporter. Secretion signal and promoter identities had significant effects on secretion output. This library further enabled a 28-fold improvement of binding activity of Sb-secreted haPD-1, an established anti-tumor immunotherapeutic, and improved haPD-1 detection in mouse stool samples following oral gavage of Sb_haPD-1. Sb secretion trends of both GLuc and haPD-1 in vitro mirrored payload expression in vivo. This protein secretion library toolkit will serve as a valuable resource to rapidly optimize protein therapeutic output from engineered Sb.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945789","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}
Maxence Holtz, Simon D'Oelsnitz, Cecília Castellví Domingo, Niklas G Madsen, Mars Yu Hong, Jonathan Asmund Arnesen, Aafke C A van Aalst, Samantha de Haan, Christopher K Weingarten, Ditte H Welner, Pamela A Silver, Yan Jessie Zhang, Michael K Jensen, Carlos G Acevedo-Rocha
{"title":"Engineering biosensors to enhance monoterpene indole alkaloid production in yeast.","authors":"Maxence Holtz, Simon D'Oelsnitz, Cecília Castellví Domingo, Niklas G Madsen, Mars Yu Hong, Jonathan Asmund Arnesen, Aafke C A van Aalst, Samantha de Haan, Christopher K Weingarten, Ditte H Welner, Pamela A Silver, Yan Jessie Zhang, Michael K Jensen, Carlos G Acevedo-Rocha","doi":"10.1016/j.tibtech.2026.08.011","DOIUrl":"10.1016/j.tibtech.2026.08.011","url":null,"abstract":"<p><p>Monoterpene indole alkaloids (MIAs) are medicinally valuable plant natural products, but their scarcity and structural complexity hinder conventional production. Microbial cell factories offer a sustainable alternative, although optimization of their long biosynthetic pathways is constrained by costly, low-throughput analytics. In this article, we evolved the promiscuous bacterial transcription factor RamR to detect five MIAs, obtaining sensitive and selective biosensor variants with EC<sub>50</sub> values below 10 μM. We functionalized RamR in yeast and used it to screen a 188-gene overexpression library for improved strictosidine (STR) production, the common precursor for all MIAs. Biosensor fluorescence strongly correlated with HPLC measurements (R<sup>2</sup> = 0.932), enabling identification of engineering targets that, when combined, increased STR titers more than threefold to over 220 mg/l. This RamR-based biosensing platform enables cost-effective screening and makes large biological design spaces experimentally accessible, accelerating strain and enzyme engineering for MIAs and other complex natural products.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920457","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}
Sanne M de Smit, Largus Lars T Angenent, Federico Aulenta, Abraham Esteve-Nunez, Albert Guisasola, Falk Harnisch, Elizabeth S Heidrich, Ludovic Jourdin, Marika Kokko, Rikke Linssen, Deepak Pant, Catarina M Paquete, Jo Philips, Sebastià Puig, Korneel Rabaey, Miriam A Rosenbaum, Uwe Schröder, Tom Sleutels, César I Torres, Marianna Villano, Annemiek Ter Heijne
{"title":"An electrified future with microbial electrochemical technologies: how to realize the dream?","authors":"Sanne M de Smit, Largus Lars T Angenent, Federico Aulenta, Abraham Esteve-Nunez, Albert Guisasola, Falk Harnisch, Elizabeth S Heidrich, Ludovic Jourdin, Marika Kokko, Rikke Linssen, Deepak Pant, Catarina M Paquete, Jo Philips, Sebastià Puig, Korneel Rabaey, Miriam A Rosenbaum, Uwe Schröder, Tom Sleutels, César I Torres, Marianna Villano, Annemiek Ter Heijne","doi":"10.1016/j.tibtech.2026.07.031","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.031","url":null,"abstract":"<p><p>Microbial electrochemical technologies (METs) are emerging with innovative applications in various fields by harnessing the combined action of electrodes and microbes. What if METs could be the key to circularity in wastewater treatment? What if METs could be employed to convert electricity and CO<sub>2,</sub> or waste, into valuable organics? What if new bioinspired materials could be produced through METs? What if METs could be used as smart bio-based sensors? We provide our vision for the future of METs in four sectors: water treatment, industrial biotechnology, electronics, and biosensors. We showcase why and how METs could advance or replace state-of-the-art technologies and discuss the challenges that must be overcome to make METs part of an electrified future powered by microbes.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920271","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}
Jooyeon Suh, Geunho Yook, Junhan Bae, Sehan Jeong, Somin Kim, June Hyuk Kim, Hyun Guy Kang, Ming-Ru Wu, Yi-Jun Kim, Jin-Hong Kim
{"title":"A logic-gated synthetic circuit coupled with microenvironmental reprogramming overcomes immune exclusion in antigen-poor chondrosarcoma.","authors":"Jooyeon Suh, Geunho Yook, Junhan Bae, Sehan Jeong, Somin Kim, June Hyuk Kim, Hyun Guy Kang, Ming-Ru Wu, Yi-Jun Kim, Jin-Hong Kim","doi":"10.1016/j.tibtech.2026.08.008","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.008","url":null,"abstract":"<p><p>Chondrosarcoma remains refractory to immunotherapy due to a paucity of targetable antigens and a suppressive tumor microenvironment (TME). We developed a modular strategy integrating tumor-intrinsic genetic logic with rational TME reprogramming to overcome these barriers. Using a 57,715-element massively parallel reporter assay, we identified chondrosarcoma-selective synthetic promoters and engineered a Boolean AND-gate circuit that ensures high-fidelity expression of a surface T cell engager exclusively within malignant cells. To further address the immunosuppressive TME, we identified macrophage migration inhibitory factor (MIF) as a target for blockade. Single-cell RNA sequencing in human PBMC-reconstituted chondrosarcoma xenograft models revealed that the circuit initiates T cell activation, while MIF blockade prevents exhaustion by promoting proliferative T cells and M1-polarized macrophages. Local administration induced a systemic abscopal effect, regressing distant, untreated tumors. Collectively, these findings provide a programmable blueprint for converting immunologically cold, antigen-poor malignancies into systemically immune-responsive states.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907299","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}
Masoud Khazaei, Muamer Dervisevic, Nicolas H Voelcker
{"title":"Sensing the future of cell therapy manufacturing.","authors":"Masoud Khazaei, Muamer Dervisevic, Nicolas H Voelcker","doi":"10.1016/j.tibtech.2026.08.010","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.010","url":null,"abstract":"<p><p>Cell therapies are increasingly manufactured in closed, automated culture systems, yet decisions about cell quality, safety, and release still rely largely on sparsely executed, destructive, and offline assays. Over the past 5 years, significant progress has been made in developing biosensors capable of real-time measurement of key biochemical and physicochemical indicators including metabolites, ionic species, and protein-associated stress indicators within cell culture environments. However, most systems remain disconnected from manufacturing workflows and fail to support actionable process control. This opinion article discusses the next phase of innovation and the need to reposition biosensors as process analytical technology, shifting the field from descriptive monitoring toward integrated, decision-driven control of cell therapy manufacturing.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888625","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":"Beyond statutory compliance: toward comprehensive genomic governance.","authors":"Guillermo Aquino-Jarquin","doi":"10.1016/j.tibtech.2026.08.009","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.009","url":null,"abstract":"<p><p>I welcome the discussion raised by Hernández-Huerta and colleagues. While legal provisions regulating the transfer of biological materials are significant, genomic governance goes beyond mere legal compliance. It encompasses transparency, accountability, benefit-sharing, and long-term stewardship. Recent international recommendations emphasize the need for comprehensive governance frameworks for national genomic initiatives.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888641","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":"Advancing European standards and regulations for 3D bioprinting.","authors":"Ambra Maddalon, Giulia Leonetti, Sophie Zimmer","doi":"10.1016/j.tibtech.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.001","url":null,"abstract":"<p><p>3D bioprinting has the potential to provide nonanimal alternatives to preclinical testing and revolutionize current clinical and transplantation practices. Realizing this potential requires a concerted effort to develop and advance European standards and regulatory frameworks, ensuring a clear and safe pathway for the clinical integration of 3D bioprinting.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888568","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 : 2026-09-01Epub Date: 2026-01-22DOI: 10.1016/j.tibtech.2025.12.010
Yong Wang, Wei-Cheng Yang, Patrick De Clercq, Norman C Leppla, Adeney de Freitas Bueno, Ricardo Ramirez-Romero, Nicolas Desneux, Lian-Sheng Zang
{"title":"Biotechnology-driven artificial diets for mass-rearing arthropod natural enemies.","authors":"Yong Wang, Wei-Cheng Yang, Patrick De Clercq, Norman C Leppla, Adeney de Freitas Bueno, Ricardo Ramirez-Romero, Nicolas Desneux, Lian-Sheng Zang","doi":"10.1016/j.tibtech.2025.12.010","DOIUrl":"10.1016/j.tibtech.2025.12.010","url":null,"abstract":"<p><p>Arthropod natural enemies are central to biological control programs, where they regulate pest populations while contributing to ecological stability and biodiversity conservation. Nonetheless, for many species, large-scale rearing of these arthropods is constrained by expensive, labor-intensive methods that still rely heavily on living hosts. Emerging biotechnological tools promise to transform rearing practices by supporting the design of accurate, affordable, and host-independent artificial diets for arthropod natural enemies. This review explores biotechnology-driven advances in nutrient profiling, low-cost production, and functional packaging and integrates them into a unified framework. Moreover, this review highlights how the integration of multidisciplinary approaches and biotechnological innovations can address critical challenges in artificial diet development to enable sustainable biocontrol pest management at practical scales.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2530-2544"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041762","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 : 2026-09-01Epub Date: 2026-02-14DOI: 10.1016/j.tibtech.2025.12.026
Panagiota M Kalligosfyri, Antonella Miglione, Ada Raucci, Wanda Cimmino, Gabriella Iula, Alessandra Glovi, Sima Singh, Michelino De Laurentiis, Antonio Giordano, Stefano Cinti
{"title":"Multifunctional biosensors redefining liquid biopsy: advancing simultaneous multianalyte detection.","authors":"Panagiota M Kalligosfyri, Antonella Miglione, Ada Raucci, Wanda Cimmino, Gabriella Iula, Alessandra Glovi, Sima Singh, Michelino De Laurentiis, Antonio Giordano, Stefano Cinti","doi":"10.1016/j.tibtech.2025.12.026","DOIUrl":"10.1016/j.tibtech.2025.12.026","url":null,"abstract":"<p><p>Liquid biopsy has revolutionized noninvasive disease diagnosis and monitoring by detecting circulating biomarkers such as tumor-derived DNA, miRNAs, proteins, exosomes, and circulating tumor cells in body fluids. Conventional single-analyte approaches fail to capture disease complexity, limiting diagnostic accuracy. Multifunctional biosensors enable simultaneous detection of multiple biomarkers, representing a paradigm shift in liquid biopsy. This review highlights recent advances in diverse detection strategies, including optical, electrochemical, plasmonic, and clustered regularly interspaced short palindromic repeats-based assays, alongside innovations in hybrid platforms, smart surface engineering, and nanotechnology. We also discuss integration with microfluidics, artificial intelligence, and chemometric analysis to enhance sensitivity, reduce signal interference, and improve scalability. Finally, challenges in clinical translation and standardization are highlighted, underscoring the transformative potential of multifunctional biosensors in precision medicine and early disease detection.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2577-2595"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198116","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":"Thermotolerant yeasts and their biotechnological applications.","authors":"Roksolana Vasylyshyn, Justyna Ruchala, Kostyantyn Dmytruk, Andriy Sibirny","doi":"10.1016/j.tibtech.2025.12.025","DOIUrl":"10.1016/j.tibtech.2025.12.025","url":null,"abstract":"<p><p>Most known yeasts are mesophilic organisms, with optimal growth at 28-30°C. However, a few species, notably Ogataea polymorpha and Kluyveromyces marxianus, can grow at temperatures around 50°C. Their thermotolerance is of both fundamental and applied interest, offering advantages for high-temperature bioprocesses. Notably, cultivation at elevated temperatures facilitates simultaneous saccharification and fermentation (SSF) of starchy and lignocellulosic substrates, reduces sterility requirements, lowers distillation costs, and enhances the rates of biochemical reactions. These features make thermotolerant yeasts attractive platforms for producing biofuels, proteins, and other valuable compounds. Despite their potential, the underlying mechanisms of thermotolerance in these species remain underexplored. Herein, we systematically review the molecular, cellular, and metabolic mechanisms underlying yeast thermotolerance and discuss their implications for high-temperature industrial biotechnology.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2563-2576"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284995","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}