{"title":"Multienzyme cascades for non-grain carbon feedstocks valorization: Recent advances and perspectives.","authors":"Xin Wang, Huan Chen, Chun-Jiang Ma, Jing-Jing Zhang, Feng Cheng, Ya-Ping Xue, Yu-Guo Zheng","doi":"10.1016/j.biotechadv.2026.109082","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.109082","url":null,"abstract":"<p><p>Biomanufacturing is increasingly transitioning toward sustainable non-grain carbon feedstocks, including gaseous C1 compounds, liquid C1 substrates, and solid non-grain biomass. However, the efficient utilization of these feedstocks remains hindered by mass-transfer limitations, thermodynamic constraints, substrate and intermediate cytotoxicity, and the inherent physical limitations of macromolecular catalysts. Intracellular multienzyme cascade catalysis offers a promising solution by organizing highly coordinated catalytic networks within living cells, thereby enhancing metabolic efficiency and overcoming multiple bioconversion barriers. In this review, we systematically analyze the mechanisms and engineering strategies underlying whole-cell cascade systems from the integrated perspectives of material, energy, and information flows. Based on these principles, we propose a universal diagnostic and design framework for the bioconversion of non-grain carbon feedstocks. We further illustrate how these general design rules can be tailored and implemented at the systems level for the efficient conversion of specific substrate classes. In addition, we highlight the emerging role of artificial intelligence in enabling predictive system reconstruction through generative design, global pathway optimization, and automated design-build-test-learn (DBTL) cycles. Collectively, this review establishes a unified theoretical and practical framework for the rational design of next-generation biomanufacturing platforms based on intracellular multienzyme cascade catalysis.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109082"},"PeriodicalIF":14.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227161","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}
Michael N Wiafe, Farhan Ahmad, Ashenafi Berhanu, Mudassir A Dar, Yue Bai, Daochen Zhu
{"title":"Termite-microbiome symbiosis as a bioreactor model for lignocellulosic biomass pretreatment and biorefinery.","authors":"Michael N Wiafe, Farhan Ahmad, Ashenafi Berhanu, Mudassir A Dar, Yue Bai, Daochen Zhu","doi":"10.1016/j.biotechadv.2026.109080","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.109080","url":null,"abstract":"<p><p>Lignocellulosic biomass conversion is still limited by pretreatment strategies that are energy-intensive, chemically harsh, and difficult to scale. In contrast, termites and their symbiotic microbiota represent one of the most efficient natural systems for lignocellulose deconstruction, achieving rapid biomass conversion under mild physicochemical conditions. This review synthesizes current knowledge on termite-bacteria symbiosis and interprets it from a bioprocess engineering perspective, positioning it as a model for the design of engineered lignocellulosic biorefineries. By integrating gut compartmentalization, microbial community organization, enzymatic repertoires, and interaction networks, we develop a systems-level view of how spatial organization, physicochemical gradients, and cooperative metabolism jointly enable efficient biomass processing. Comparative analysis with conventional microbial platforms and industrial pretreatment technologies highlights the process advantages of termite-inspired systems in energy demand, process integration, and scalability. Rather than providing a purely descriptive synthesis, this review translates biological organization into engineering logic, outlining practical design principles for reactor architecture, consortium assembly, and enzyme deployment. We further identify key bottlenecks that constrain industrial translation, including transport limitations, gradient control, and community stability. Together, these insights provide a structured foundation for the rational development of robust, scalable, and sustainable termite-inspired lignocellulosic bioprocesses.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109080"},"PeriodicalIF":14.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227102","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":"Evolutionary logic and biotechnological potential of alternative splicing in higher eukaryotes: Comparative insights from plants and animals.","authors":"Zhongwu Zhou, Il-Hoon Cho, Ulhas S Kadam","doi":"10.1016/j.biotechadv.2026.109077","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.109077","url":null,"abstract":"<p><p>Alternative splicing (AS) generates transcript and protein isoforms, but its evolutionary significance cannot be inferred from isoform number alone. This review uses a comparative evidence framework to separate splice-variant origin, functional consequence, and evolutionary retention in plants and animals. We synthesize evidence from long-read sequencing, single-cell isoform profiling, pangenomics, proteogenomics, and perturbation studies. Animal studies emphasize exon-level switches in neural, cardiac, immune, and germline programs, whereas plant studies highlight intron retention, exitron splicing, environmental responses, and polyploidy-associated regulation. These are tendencies shaped by biological and sampling differences, not exclusive properties of either kingdom. Three worked examples illustrate how reproducible regulation, conservation or population evidence, molecular consequences, and targeted perturbation support different levels of inference. Functional effects alone do not establish historical adaptation, and conservation alone does not identify the trait under selection. The framework helps prioritize isoforms for crop improvement, biomarkers, and RNA intervention. Clinical splice modulation and field-evaluated natural rice alleles demonstrate translational potential, while highlighting the distinction between validated outcomes and prospective engineering. Future studies should connect isoform-resolved measurements to causal perturbation and fitness or agronomic performance across relevant environments.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109077"},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191291","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":"Engineering the microbial architects: a genetic revolution in bio-electrochemical hydrogen production.","authors":"Pankaj Kumar, Stuti Sharma, Sakshi, Abhishek Rana, Manisha Vaidya, Ashish Kumar, Lakhveer Singh","doi":"10.1016/j.biotechadv.2026.109076","DOIUrl":"10.1016/j.biotechadv.2026.109076","url":null,"abstract":"<p><p>Microorganisms, endowed with extraordinary metabolic versatility and environmental adaptability, represent a transformative frontier for addressing global sustainability imperatives. Engineering microbial systems through regulatory network rewiring and synthetic biology-driven functional augmentation substantially amplifies their biotechnological utility. Herein, we review the convergence of synthetic biology, bio-electrocatalysis, and reactor engineering as an integrated framework for sustainable biohydrogen production. Comparative analysis with conventional hydrogen generation strategies underscores the superiority of bioelectrochemical systems (BESs), which simultaneously enable wastewater valorisation and clean hydrogen production through microbially driven electron transfer cascades. Moreover, the mechanistic electron generation-to-hydrogen conversion continuum highlights the indispensable dominance of biotic catalysis. Furthermore, CRISPR-Cas9-mediated multiplex genome editing is examined as a precision tool surpassing traditional mutagenesis approaches for pathway optimisation. Key electrogenic taxa, their electrochemical interfaces and influences within BESs architectures, prevailing technological bottlenecks in scalability, techno-economic feasibilitites and forward-looking strategies toward wholly biological, scalable hydrogen production systems are critically featured.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109076"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179320","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":"From base transitions to expanded editing tools: development and applications of plant base editors.","authors":"Ning Sui, Jiekun Zhang, Wenyue Xu, Meixin Pang, Ruixiang Zhang, Nan Chai, Jun Wen, Taoli Liu, Zhiye Zheng, Jingyang Huang, Tianlin Tang, Hongfu Quan, Jianping Luo, Yuying Huang, Xiuping Wei, Zhiyong Zhang, Yao-Guang Liu, Qinlong Zhu, Dongchang Zeng","doi":"10.1016/j.biotechadv.2026.109074","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.109074","url":null,"abstract":"<p><p>Plant base editing enables targeted nucleotide substitutions and provides a powerful approach for functional genomics and crop improvement. The toolkit has expanded from canonical cytosine and adenine editors to dual-base, transversion, Cas12-based, and organelle-targeted systems, broadening the range of accessible mutations and genomic targets. These advances create new opportunities for generating useful alleles, modifying gene function, and enabling directed evolution. However, expanded base-editing capabilities do not necessarily ensure predictable outcomes or successful breeding applications. This review summarizes the development of plant base editors, computational tools for target design, and their applications in crop research. We examine editor architectures and compare editing efficiency, product purity, and specificity, with particular attention to transversion editing. We also highlight the intrinsic technical limitations of base editors and the bottlenecks encountered when moving from laboratory research to field applications. By connecting base editor development with practical constraints, this review provides guidance for editor selection and identifies priorities for applying base editing to crop improvement.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109074"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179378","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}
Boming Cui, Xintao Lian, Weiwei Song, Hua Yang, Xiaojuan Yang, Lan Wang, Ge Yang
{"title":"Beyond SELEX: AI-driven aptamers from sequence to structure to function.","authors":"Boming Cui, Xintao Lian, Weiwei Song, Hua Yang, Xiaojuan Yang, Lan Wang, Ge Yang","doi":"10.1016/j.biotechadv.2026.109075","DOIUrl":"10.1016/j.biotechadv.2026.109075","url":null,"abstract":"<p><p>Conventional aptamer discovery by systematic evolution of ligands by exponential enrichment (SELEX) is often constrained by limited library capacity, PCR bias, and multi-round screening. The recent convergence of artificial intelligence with aptamer development is driving a paradigm shift from empirical screening toward rational, data-driven design. This Review presents a timely and comprehensive overview of AI integration across the entire aptamer development pipeline, with a particular emphasis on advances reported in 2024-2026. We begin by discussing bioinformatics databases and computational tools for high-throughput SELEX data analysis. We then review state-of-the-art strategies for secondary and tertiary structure prediction, including recent breakthroughs such as AlphaFold 3, RoseTTAFoldNA, and diffusion-based approaches. We also cover machine learning methods for aptamer-target interaction prediction, molecular docking, dynamics simulations, and free energy calculations. A major focus is placed on very recent AI-driven generative design, including diffusion models (AptaDiff), language model-based frameworks (InstructNA, GRAPE-LM), and reinforcement learning approaches (AiDTA) for de novo aptamer generation and optimization. Emerging applications of AI-designed aptamers in precision diagnostics, targeted therapy, and biosensing are also surveyed. Finally, we discuss current challenges and outline future directions toward closed-loop, interpretable AI frameworks for translational aptamer development. By synthesizing the latest computational and experimental advances, this Review aims to serve as a timely resource for researchers seeking to leverage AI for next-generation aptamer discovery.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109075"},"PeriodicalIF":14.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179357","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}
Yi Li, Yufan Xing, Ziyue Wang, Yan He, Zihan Wang, Ziru Yuan, Xuanni Zheng, Zishun Cheng, Mingfeng Cao, Jun Ni, Hongting Tang
{"title":"Programmable plant chassis for sustainable biomanufacturing of high-value natural products.","authors":"Yi Li, Yufan Xing, Ziyue Wang, Yan He, Zihan Wang, Ziru Yuan, Xuanni Zheng, Zishun Cheng, Mingfeng Cao, Jun Ni, Hongting Tang","doi":"10.1016/j.biotechadv.2026.109044","DOIUrl":"10.1016/j.biotechadv.2026.109044","url":null,"abstract":"<p><p>Biomanufacturing has emerged as a strategic emerging industry worldwide, offering sustainable alternatives to conventional chemical manufacturing. To support this development, diverse production chassis have been developed, including microorganisms, mammalian cell culture systems, and plant-based platforms. Among these, plants represent a promising chassis for the biosynthesis of high-value products, as they directly fix CO₂ through photosynthesis and possess sophisticated metabolic networks that facilitate the production of structurally complex molecules. Recent advances in synthetic biology have increased the programmability of plant systems and enabled their development as engineered production chassis for the production of high-value products. This review integrates recent advances in natural and synthetic genetic elements including promoters, terminators, and transcription factors (TFs) that facilitate chassis development are summarized. Recent advances in the elucidation, reconstruction, and optimization of biosynthetic pathways for representative classes of valuable compounds, including alkaloids, terpenoids, and phenylpropanoids, are then highlighted, with particular emphasis on pathway engineering strategies that enhance productivity. Finally, we outline the key challenges and future perspectives for the large-scale industrial applications of plant chassis. This review provides a comprehensive and timely perspective on plant-based biomanufacturing, offering conceptual guidance and practical insights for advancing plant chassis from laboratory research to sustainable industrial applications.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"109044"},"PeriodicalIF":14.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966442","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}
Brett Metcalfe,Jasper J. Koehorst,Theodore Dalamagas,Georgios K. Georgakilas,Antonis Kokossis,Vitor A.P. Martins dos Santos,Michael J. O'Donohue
{"title":"IBISBA: Digitalisation to empower biotechnology and drive biomanufacturing","authors":"Brett Metcalfe,Jasper J. Koehorst,Theodore Dalamagas,Georgios K. Georgakilas,Antonis Kokossis,Vitor A.P. Martins dos Santos,Michael J. O'Donohue","doi":"10.1016/j.biotechadv.2026.109031","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2026.109031","url":null,"abstract":"","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"41 1","pages":"109031"},"PeriodicalIF":16.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021070","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}