Xin Ni, Haoyu Wang, Mengyao Zhang, Ning Gao, Jiaoqi Gao, Fan Yang, Yongjin J Zhou
{"title":"Creating a glycolysis-minimized central metabolism for efficient biosynthesis and cell growth in yeast.","authors":"Xin Ni, Haoyu Wang, Mengyao Zhang, Ning Gao, Jiaoqi Gao, Fan Yang, Yongjin J Zhou","doi":"10.1016/j.tibtech.2026.07.020","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.020","url":null,"abstract":"<p><p>Long-term natural evolution has selected glycolysis as the major metabolic mode to generate energy and cellular building blocks for rapid cell growth in eukaryotes such as yeast; however, glycolysis lacks a sufficient NADPH supply to drive the biosynthesis of reduced chemicals. Industrially feasible cell factories often require the most energy-economical pathway for the high-level production of target products. In this study, we successfully established a pentose phosphate pathway-dominant, glycolysis-minimized central metabolic mode in yeast, which significantly improved the cellular energy status compared with glycolysis and provided a balanced supply of ATP and NADPH. More importantly, we discovered a global carbon metabolism regulator, which drives metabolic flux toward glycolysis for energy generation, and whose disruption relieved the tight regulation of metabolic flux distribution and significantly enhanced the cellular energy status, which in turn improved the production of the energy-intensive molecules free fatty acids (FFAs) by 63%. The final engineered strain produced FFAs at a titer of 41.7 g/l, the highest titer reported for yeast fermentation. Our work provides valuable insights into the metabolic regulatory mechanisms of microorganisms.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798419","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}
Margarida M A Sacramento, Luís Henrique Reichembach, João M M Rodrigues, João F Mano
{"title":"From liquid precursors to adhesive platforms: coacervates as dynamic interface biomaterials for biotechnology.","authors":"Margarida M A Sacramento, Luís Henrique Reichembach, João M M Rodrigues, João F Mano","doi":"10.1016/j.tibtech.2026.07.028","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.028","url":null,"abstract":"<p><p>Achieving robust adhesion in wet and biological environments remains a major challenge in biotechnology and medicine. Coacervates are emerging as versatile adhesive platforms that function effectively under hydrated conditions. Their fluid-like nature enables efficient spreading at interfaces, while subsequent mechanical reinforcement stabilizes adhesion without permanent curing. In this review, we present a unifying framework in which adhesion arises from the interplay of interfacial wetting, multivalent interactions, viscoelastic energy dissipation, and kinetic arrest. We discuss how designing phase behavior and arrest dynamics can transform coacervates into functional bioadhesive interfaces for tissue sealing, drug delivery, and biointerface engineering. Finally, we outline challenges in predictive design, spatiotemporal control over arrest, and clinical translation, highlighting adhesive coacervates as multifunctional materials for complex wet environments.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798430","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}
Merna Magdy, Justin R Gibson, Abishek Dhungana, Ashley Herring-Nicholas, Renee N Cottle, Eric A Josephs
{"title":"On-target and off-target activities of CRISPR therapeutics across scales.","authors":"Merna Magdy, Justin R Gibson, Abishek Dhungana, Ashley Herring-Nicholas, Renee N Cottle, Eric A Josephs","doi":"10.1016/j.tibtech.2026.07.015","DOIUrl":"10.1016/j.tibtech.2026.07.015","url":null,"abstract":"<p><p>Recent FDA-approved gene-editing therapies illustrate not only the transformative potential of biotechnologies using CRISPR (clustered regularly interspaced short palindromic repeats)-derived ribonucleoproteins in treating a broad range of diseases but also the spectrum of possible molecular variations CRISPR therapeutics can adopt. These include exagamglogene autotemcel, an ex vivo therapy for hemoglobinopathies using CRISPR nuclease Cas9, and kayjayguran abengcemeran, an in vivo therapy using a protospacer adjacent motif-altered base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. In this opinion article, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing 'on-target' and 'off-target' mutational activities across the diverse contexts in which they occur.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13509143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amy H Lee, Khanh T M Tran, Alexander Hostetler, Kewen Lei, Jinbi Tian, Sevinj Mursalova, Alicia Lau, Gary W Liu, Charles Gorelick, Darrell J Irvine, Robert Langer, Ana Jaklenec
{"title":"Cryopreservation of cell-based therapies with enhanced cell viability and therapeutic efficacy.","authors":"Amy H Lee, Khanh T M Tran, Alexander Hostetler, Kewen Lei, Jinbi Tian, Sevinj Mursalova, Alicia Lau, Gary W Liu, Charles Gorelick, Darrell J Irvine, Robert Langer, Ana Jaklenec","doi":"10.1016/j.tibtech.2026.07.019","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.019","url":null,"abstract":"<p><p>Biobanking has played an important role in advancing cell therapy by enabling long-term preservation of cell function, facilitating product transport, and allowing flexibility in infusion scheduling. However, conventional cryopreservation methods rely on high concentrations of dimethyl sulfoxide (DMSO) and serum, which can lead to toxicity, compromise cell viability, complicate post-thaw handling (such as DMSO removal), require additional quality testing, and ultimately reduce therapeutic efficacy. We present a cryopreservation strategy that uses electroporation to introduce protective sugars intracellularly, termed sugar augmented freezing by electroporation (SAFE). Applied across multiple cell types-including chimeric antigen receptor T cells and stem cells-SAFE improved post-thaw viability and expansion by 1.8-fold and enhanced therapeutic efficacy by two-fold compared with standard cryopreservation. Furthermore, SAFE preserved proliferation-associated proteins and metabolites more effectively. Post-thaw cells maintained, and often exceeded, the functional performance of conventionally preserved cells. This work highlights the importance of optimizing cryogenic parameters to achieve greater post-thaw consistency, scalability, and clinical impact on next-generation cell-based therapies.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798355","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}
Yan-Ruide Li, Haochen Nan, Youcheng Yang, Shubing Wang, Lili Yang
{"title":"In situ programming of unconventional T cells.","authors":"Yan-Ruide Li, Haochen Nan, Youcheng Yang, Shubing Wang, Lili Yang","doi":"10.1016/j.tibtech.2026.07.027","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.027","url":null,"abstract":"<p><p>Unconventional T cells (UTCs), including γδ T cells, mucosal-associated invariant T cells, and natural killer T cells, recognize conserved nonpeptide antigens through semi-invariant T cell receptors in an human leukocyte antigen-independent manner, making them attractive candidates for broadly applicable immunotherapies. However, their clinical translation remains limited by poor spatiotemporal control of activation, functional exhaustion, and insufficient tissue homing in vivo, particularly in solid tumors. Biomaterial-based delivery systems provide a promising strategy to overcome these barriers by enabling localized and sustained delivery of UTC ligands, cytokines, and nucleic acids within diseased tissues. Through precise in situ programming of UTC responses, these platforms may enhance therapeutic efficacy and safety. This review summarizes current biomaterial-based strategies and discusses emerging opportunities for in situ UTC programming in human cancers.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765676","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":"Empowering microbes with natural armor: encapsulation strategies for agri-food and biotech innovations.","authors":"Simona Cioffi, Michele Iafisco, Alessio Adamiano","doi":"10.1016/j.tibtech.2026.07.030","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.030","url":null,"abstract":"<p><p>Encapsulation enables microbial technologies across agriculture, biotechnology, and biomedicine by protecting microorganisms from environmental and process-related stresses while extending their functional performance. Natural materials, including polysaccharides such as alginate and chitosan, and biomineral nanoparticles, are emerging as key enablers of encapsulation performance, while supporting sustainability, scalability, and industrial implementation. In this review, we analyze recent advances in natural polymer- and biomineral-based encapsulation systems, focusing on how material selection, encapsulation architecture, and microbial metabolism shape engineered microenvironments. We further discuss how encapsulation becomes technologically and environmentally relevant only when functional gains justify material and processing costs. Finally, we argue for a conceptual shift in encapsulation strategies: from protective supports toward bioinspired microhabitats and living microcapsules capable of programmable microbial functions.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764732","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}
Mathilde Pinon, Per Falholt, Thomas G Schmidt, José Arnau
{"title":"Precision-fermented milk proteins as a model for industrial food biotechnology.","authors":"Mathilde Pinon, Per Falholt, Thomas G Schmidt, José Arnau","doi":"10.1016/j.tibtech.2026.07.026","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.026","url":null,"abstract":"<p><p>Dairy proteins are among the most nutritionally and functionally valuable proteins used in food, clinical nutrition, and infant nutrition, yet their supply remains structurally linked to livestock production and dairy processing streams. Precision fermentation offers, based on proven technology, a route to produce individual milk proteins independently of animal agriculture while preserving their molecular identity and application potential. Recent advances in host engineering, secretion capacity, and bioprocess optimization have moved recombinant milk proteins from proof-of-concept toward industrial relevance. However, not all milk proteins are equally tractable fermentation targets. In this opinion article, we examine β-lactoglobulin, α-lactalbumin, and caseins through the lens of nutritional value, functionality, manufacturing complexity, and commercial readiness. We argue that future success will depend less on sequence expression alone than on scalable biomanufacturing technology and know-how, post-translational fidelity, and application-driven target prioritization.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762301","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}
Christian Fink, Franziska Steger, Sebastian Schmidt, Elisa Hilts, François Unger, Aquilla Ruddyard, Maximilian Klein, Bart-Jan Akerboom, Thomas Stehrer-Polašek, Stefan Drießler, Shubham Gurav, Ross T Fennessy, Justin Smith, Günther Bochmann, Simon K-M R Rittmann
{"title":"Pilot-scale production of leucine from CO<sub>2</sub>.","authors":"Christian Fink, Franziska Steger, Sebastian Schmidt, Elisa Hilts, François Unger, Aquilla Ruddyard, Maximilian Klein, Bart-Jan Akerboom, Thomas Stehrer-Polašek, Stefan Drießler, Shubham Gurav, Ross T Fennessy, Justin Smith, Günther Bochmann, Simon K-M R Rittmann","doi":"10.1016/j.tibtech.2026.07.014","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.014","url":null,"abstract":"<p><p>Beyond their nutritional value, amino acids are of relevance in medicine and, due to their chemical properties, they are indispensable for applications in many different realms, such as pharmaceutics, cosmetics, animal feed, food, and the beverage industry. In this research article, we report an archaeal cell factory for leucine production from CO<sub>2</sub> that has been generated by rational design, random mutagenesis, and pathway engineering. The cell factory has been bioprocess-technologically examined and successfully scaled up with regard to productivity, product quality, and operational stability. In a 2-day fed-batch campaign, we produced 181 g of leucine from CO<sub>2</sub> at the 150-L pilot-plant scale with a mean volumetric leucine productivity of 65 mg L<sup>-1</sup> h<sup>-1</sup>. A thorough techno-economic analysis indicates that the rollout of leucine production from CO<sub>2</sub> is nearly economically feasible on a global scale.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763963","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}
Shiqing Li, Xin Zhang, Tinglu Yan, Yabin Liu, Yuhan Chen, Zihan Zhang, Yuanhong Zhu, Yanrong Xu, Yang Luo, Yang Liu, Neil Crickmore, Dong Fan, Fuping Song
{"title":"A Bacillus thuringiensis ΔcdsR-based expression system for insecticidal proteins identified using AlphaFold3.","authors":"Shiqing Li, Xin Zhang, Tinglu Yan, Yabin Liu, Yuhan Chen, Zihan Zhang, Yuanhong Zhu, Yanrong Xu, Yang Luo, Yang Liu, Neil Crickmore, Dong Fan, Fuping Song","doi":"10.1016/j.tibtech.2026.07.023","DOIUrl":"10.1016/j.tibtech.2026.07.023","url":null,"abstract":"<p><p>Environmentally friendly biopesticides, such as those based on the bacterium Bacillus thuringiensis (Bt), have an important role to play in Integrated Pest Management systems. An increasingly diverse range of pesticidal proteins is being discovered, led by advances in genome sequencing and the bioinformatic identification of candidate genes. In this work, we utilized an AlphaFold3-based structure-prediction approach to identify candidate genes and, in parallel, developed a Bt chassis strain that can be universally used to express new pesticidal proteins. This chassis strain is based on a cdsR deletion strain with a controllable cell death pathway that decouples toxin production from sporulation, enabling cytoplasmic hyperexpression via strong promoters and encapsulation of recombinant proteins. These characteristics provide superior efficacy, UV stability, and environmental safety compared with conventional Bt formulations. Several of the identified proteins displayed insecticidal activity when expressed in this strain, providing a versatile framework for next-generation biocontrol and sustainable pest-management innovation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725252","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}
Andreas Dimopoulos, Konstantinos Ioannidis, Nikolaos S Giakoumakis, Hanna Svitina, Charalampos Androulidakis, Dirk De Vos, Isaak Decoene, Ioannis Papantoniou
{"title":"Scalable 4D biofabrication process for the manufacture of scaffold-free bone-forming callus implants.","authors":"Andreas Dimopoulos, Konstantinos Ioannidis, Nikolaos S Giakoumakis, Hanna Svitina, Charalampos Androulidakis, Dirk De Vos, Isaak Decoene, Ioannis Papantoniou","doi":"10.1016/j.tibtech.2026.07.021","DOIUrl":"10.1016/j.tibtech.2026.07.021","url":null,"abstract":"<p><p>Critical-size long bone defects remain a major clinical challenge, with treatments such as autografts or distraction osteogenesis causing donor-site morbidity, infection, or failure to restore complex bone architecture. Tissue-engineered implants that recapitulate native fracture healing provide a promising solution. However, scalability for dense cellular constructs is lacking. To address this, we bioprinted high-cell-density implants using rheologically competent sacrificial alginate bioinks. The constructs were supported by partially crosslinked alginate during bioprinting and chondrogenic differentiation, after which selective EDTA-mediated alginate dissolution generated scaffold-free implants. Quality characterization confirmed chondro-osteogenic signatures and extracellular matrix gene upregulation. Upon in vivo implantation in immunocompromised mice, implants underwent endochondral ossification, forming cortical and trabecular bone with bone marrow compartments. Integration with a suspension bioreactor enabled production of human-sized proof-of-concept implants. This work establishes a scalable 4D biofabrication process that integrates 3D bioprinting with dissolvable sacrificial alginate bioinks and results in scaffold-free, bone-forming callus implants.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723777","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}