{"title":"Enzymatic depolymerization of lignin and electrocatalytic hydrodeoxygenation for the production of reduced aromatic compounds: A review and perspective","authors":"Maedeh Mohammadi , Anahita Soleimani , Yuheng Lin , Mahsa Alian , Hemen Hosseinzadeh , Sunil Kumar Suman , Mim Rahimi , Venkatesh Balan","doi":"10.1016/j.biotechadv.2025.108647","DOIUrl":"10.1016/j.biotechadv.2025.108647","url":null,"abstract":"<div><div>The depletion of fossil resources and growing environmental concerns have intensified the search for sustainable alternatives for fuel and chemical production. Lignin, an abundant yet underutilized component of lignocellulosic biomass, presents significant potential as a renewable source of aromatic compounds. In this review and perspective, we highlight recent advancement in lignin valorization through enzymatic depolymerization using bacterial and fungal lignin degrading enzymes, and electrocatalytic hydrodeoxygenation (ECHDO). The review delves into the structure and inherent recalcitrance of lignin, alongside the mechanisms and efficiencies of various lignin-degrading enzymes, such as peroxidases and laccases, as reported in recent studies. It also provides a critical evaluation of the principles, benefits, and progress in ECHDO for upgrading lignin-derived compounds, with a focus on reactor design, catalyst systems, and energy efficiency. Key challenges and opportunities for advancing both processes are explored, along with future directions for their integration and optimization. While these technologies are currently being investigated separately, we provide a perspective for their potential integration by highlighting key challenges and opportunities for the development of an integrated bioelectrochemical platform for sustainable lignin valorization. By synthesizing current knowledge, this comprehensive review offers valuable insights for researchers and industry professionals striving to advance the sustainable utilization of lignin within biorefineries, contributing to the advancement of the circular bioeconomy.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108647"},"PeriodicalIF":12.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663390","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}
Yu-Xin Yang , Dong-Xun Li , Rui-Yun Wang , Xiao-Jun Ji , Yue-Tong Wang , Qi Guo , Tian-Qiong Shi
{"title":"Recent advances and multiple strategies for the synthesis of terpenoid fragrances and flavors in model microorganisms","authors":"Yu-Xin Yang , Dong-Xun Li , Rui-Yun Wang , Xiao-Jun Ji , Yue-Tong Wang , Qi Guo , Tian-Qiong Shi","doi":"10.1016/j.biotechadv.2025.108646","DOIUrl":"10.1016/j.biotechadv.2025.108646","url":null,"abstract":"<div><div>Terpenoids, known for their structural and functional diversity, play a significant role in various fields such as energy, cosmetics, pharmaceuticals, and fragrances. With the increasing globalization of the fragrance and flavor market, there is an urgent need to develop microbial cell factories to sustainably produce terpenoids through fermentation using renewable raw materials. With advancements in biotechnology, constructing efficient microbial cell factories for the heterologous synthesis of terpenoids to meet production demands has become feasible. <em>Escherichia coli</em> and <em>Saccharomyces cerevisiae</em> have emerged as potential hosts for terpenoid synthesis due to their short growth cycles, well-characterized genetic backgrounds, and ease of manipulation. This review delves into the biosynthetic pathways and genome editing technologies of terpenoids, and provides a comprehensive summary of the latest production strategies, including increasing precursor flux, enzyme engineering, suppressing flux in competing pathways, alleviating cellular toxicity, optimizing substrate utilization, and improving fermentation processes. Finally, we outline the future prospects for efficiently designing cell factories specifically tailored for the production of terpenoid fragrances and flavors.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108646"},"PeriodicalIF":12.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665138","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}
Hui Wang , Zhijie Feng , Peiyuan Liu , Jing Liu , Duo Liu , Hanjie Wang
{"title":"Advances in optogenetically engineered bacteria in disease diagnosis and therapy","authors":"Hui Wang , Zhijie Feng , Peiyuan Liu , Jing Liu , Duo Liu , Hanjie Wang","doi":"10.1016/j.biotechadv.2025.108645","DOIUrl":"10.1016/j.biotechadv.2025.108645","url":null,"abstract":"<div><div>Optogenetic bacterial technology is a cutting-edge approach that combines optogenetics and microbiology, offering a transformative strategy for disease diagnosis and therapy. This synergistic merger transcends the limitations of traditional diagnostic and therapeutic methodologies in a highly controllable, accurate and non-invasive manner. In this review, we introduce the optogenetic systems developed for microbial engineering and summarize fundamental <em>in vitro</em> design principles underlying light-responsive signal transduction in bacteria, as well as the optogenetic regulation of bacterial behaviors. We address multidisciplinary solutions to the challenges in the <em>in vivo</em> applications of light-controlled bacteria, such as limited light excitation, suboptimal delivery and targeting, and difficulties in signal tracking and management. Furthermore, we comprehensively highlight the recent progress in photo-responsive bacteria for disease diagnosis and therapy, and discuss how to accelerate translational applications.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108645"},"PeriodicalIF":12.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655343","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}
Santonu K. Sanyal , Colin Scott , Veena Nagaraj , Robert Speight , F. Hafna Ahmed
{"title":"Harnessing the biomolecular mechanisms of marine biomineralisation for carbon sequestration","authors":"Santonu K. Sanyal , Colin Scott , Veena Nagaraj , Robert Speight , F. Hafna Ahmed","doi":"10.1016/j.biotechadv.2025.108644","DOIUrl":"10.1016/j.biotechadv.2025.108644","url":null,"abstract":"<div><div>Anthropogenic activities, primarily fossil fuel combustion, have increased atmospheric carbon dioxide (CO<sub>2</sub>) levels and climate change effects. Carbon dioxide removal (CDR) is now widely accepted as essential in all pathways to limit global warming in line with the Paris Agreement. Biomineralisation offers compelling and promising natural pathways for durable carbon sequestration by converting CO₂ into stable carbonate minerals, a process driven by a suite of biomolecules within bio-calcifying organisms. These processes are orchestrated by biomolecules such as proteins (e.g., carbonic anhydrase, urease, bicarbonate and calcium ion transporters, templating proteins) and polysaccharides, which regulate nucleation, crystal growth, and stabilisation within specialised microenvironments. This review provides an in-depth exploration of how diverse marine bio-calcifying organisms including corals, molluscs, foraminifera, and microbial mats leverage their unique biochemistry and physiology to regulate intra/extra cellular ion concentrations and pH, thereby enabling precise control over calcium carbonate (CaCO₃) precipitation. This review highlights the intricate molecular mechanisms that underpin natural carbon biomineralisation and examines how tools from engineering biology such as engineered enzymes, photosynthetic and ureolytic microbial consortia, and cell-free systems can be leveraged to mimic and amplify these processes for enhanced carbon capture. Bridging a deep understanding of natural calcification with advanced biotechnological tools has the potential to drive the innovation and development of powerful carbon removal technologies urgently needed to reach net zero and beyond.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108644"},"PeriodicalIF":12.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648426","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}
Di Zhang , Jinglin Liao , Shujie He , Mengyao Wang , Jian Chen , Yong Chen , Dong Liu , Hanjie Ying
{"title":"Advances in production and application technologies of minicells: A review","authors":"Di Zhang , Jinglin Liao , Shujie He , Mengyao Wang , Jian Chen , Yong Chen , Dong Liu , Hanjie Ying","doi":"10.1016/j.biotechadv.2025.108648","DOIUrl":"10.1016/j.biotechadv.2025.108648","url":null,"abstract":"<div><div>Minicells are anucleate cells formed through asymmetric division at the poles of most rod-shaped bacteria. They lack chromosomes and are incapable of reproduction. This confers on minicells unique biological advantages, such as a higher content of cardiolipin in the cell membrane, retention of metabolic activity from the parent cells, and a reduced nucleocytoplasmic ratio, making minicells promising for applications in synthetic biology, agriculture, and medicine. This review first outlines the formation mechanisms of minicells in various rod-shaped bacteria, along with their isolation methods and current production status. It then comprehensively summarizes the latest and powerful applications of minicells that do not focus solely on traditional drug delivery. Based on the biological characteristics of minicells, the review highlights their four major functions, including detoxification and tolerance, enrichment and microreactor, molecular encapsulation and delivery, and native structural characterization. Finally, the challenges and future prospects of minicells in biotechnological applications are discussed.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108648"},"PeriodicalIF":12.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648425","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}
Ushasree Mrudulakumari Vasudevan , Laurence Soussan , Alfred Fernández-Castané , Stephan Noack , Alan D. Goddard
{"title":"Yeast as C1 cell factory: Transforming methanol and Formate into high-value compounds","authors":"Ushasree Mrudulakumari Vasudevan , Laurence Soussan , Alfred Fernández-Castané , Stephan Noack , Alan D. Goddard","doi":"10.1016/j.biotechadv.2025.108641","DOIUrl":"10.1016/j.biotechadv.2025.108641","url":null,"abstract":"<div><div>Microbial transformation of greenhouse gases, such as carbon dioxide and methane, into valuable biochemicals appears as a key strategy to sustainably decarbonize manufacturing industries. Numerous unresolved technological constraints still hamper the industrial adoption of these single‑carbon (C1) gas-based bioprocesses. Conversion of these gases into liquid C1 compounds like methanol and formate helps to reduce emissions and close the carbon loop. Certain industrial yeasts possess intrinsic capabilities to tolerate and assimilate methanol and formate, which opens an attractive route to eco-efficiently valorise these compounds. To increase the C1-based biomanufacturing potential of yeasts, synthetic methylotrophy has been developed in versatile non-methylotrophic chassis. Strategic non-rational genome engineering and strain evolutions combined with rational designs brings to light hidden C1-pathways and mechanisms of substrate tolerance. Developments in methanol-based bioproduction include simple organic acids with clear promise for industrial scale-up as well as proof-of-concept investigations of complex polyketides with intricate pathways. Recent advances in bioproduction have demonstrated encouraging results from techniques such as modular co-culture engineering and peroxisomal coupling of biosynthetic pathways with C1 metabolism. Formate-based growth and biosynthesis in yeasts is in its early stages but holds the potential to be transformative in the coming decade. This review discusses the advances, challenges, and future perspectives in methanol-based biomanufacturing and innovative initiatives in formatotrophy in yeasts. Although it is a long way off, developments in synthetic biology assisted evolutionary engineering and artificial pathways will fill up the gaps in the scalability of C1-based bioprocesses, transforming yeasts into a reliable, climate-neutral, and resource-efficient platform for the green bioeconomy of the future.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108641"},"PeriodicalIF":12.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614711","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}
Yash Mathur, Arunabh Choudhury, Sneh Prabha, Mohammad Umar Saeed, Md Nayab Sulaimani, Taj Mohammad, Md. Imtaiyaz Hassan
{"title":"Current advancement in AI-integrated drug discovery: Methods and applications","authors":"Yash Mathur, Arunabh Choudhury, Sneh Prabha, Mohammad Umar Saeed, Md Nayab Sulaimani, Taj Mohammad, Md. Imtaiyaz Hassan","doi":"10.1016/j.biotechadv.2025.108642","DOIUrl":"10.1016/j.biotechadv.2025.108642","url":null,"abstract":"<div><div>Artificial intelligence (AI) has grown in prominence over the decade and continues to advance frighteningly. With additional research in the computer hardware field, the accuracy and precision of AI models will increase exponentially. The interdisciplinary nature of AI expands the possibility of application in every field of study. The use of AI in human healthcare has also been on the rise, with the involvement of interactive models. Since drug development is a prominent part of the field, there are bound to be AI models capable of improving parameters and predictions for various techniques. This review explores the recent developments in the applications of AI in the scope of drug discovery. Focusing on the workflow of a standard interdisciplinary drug discovery approach, this review aims to provide information about various AI-enabled tools in the field. We begin with an in-depth overview of the different AI models and architectures frequently employed in the field. Next, we reviewed the applications of AI in drug discovery, discussing the state-of-the-art models and tools employed for topics such as data analysis, functional annotation, virtual screening, clinical trial optimization, and much more. Discussing the prospects, challenges, and limitations that the field faces, this review attempts to encompass the essence of AI-based drug discovery. We anticipate this review will aid the innovation of more brilliant AI tools for various subtopics of the drug discovery and development field.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108642"},"PeriodicalIF":12.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607209","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}
Ming Teng , Xiaomin Luo , Jiang Chang , Chen Yang , Xiaomeng Zhang , Liuying Li , Xudan Liu , Ruizhi Zhi , Xu Guo , Xinhua Liu
{"title":"Engineering encapsulated living bacteria for advanced healthcare management","authors":"Ming Teng , Xiaomin Luo , Jiang Chang , Chen Yang , Xiaomeng Zhang , Liuying Li , Xudan Liu , Ruizhi Zhi , Xu Guo , Xinhua Liu","doi":"10.1016/j.biotechadv.2025.108640","DOIUrl":"10.1016/j.biotechadv.2025.108640","url":null,"abstract":"<div><div>Bacterial therapies are emerging as promising alternatives to conventional treatments, particularly in the areas of intestinal therapy, oncology, and wound management. However, gastric acid, bile salts, immune cells, and reactive oxygen species in the human body hinder the colonization and growth of foreign probiotics, thereby compromising the efficacy of bacteriotherapy. Recent advancements in engineering encapsulated live bacteria strategies utilizing biopolymers to construct protective shells on the bacterial surface to significantly address the aforesaid challenges have gained unprecedented attention. The scrumptious integration of multiple probiotic species, bioencapsulation biomaterials, and on-demand encapsulation technologies offers tremendous advantages over conventional living bacterial counterparts, such as precise targeting, rapid immune activation, and synergistic therapeutic effects. This review presents the essential natures and response mechanism selectivity for encapsulation biomaterials from the design perspective of engineered bacterial therapeutics, including pH-responsive, enzyme-responsive, and reactive oxygen species (ROS)-responsive materials. Engineering bacterium requires a uniquely tailored design strategy within the polymer-targeted delivery platform. Meanwhile, the review provides an account of its recent developments and advancements in the biomedical fields, with emphasis on tissue repair, anti-inflammatory, antibacterial, anti-tumor, and other therapeutic applications. Finally, challenges and emerging trends in its clinical translation are expounded. By highlighting the potential of bacteria to revolutionise the therapeutic landscape, this review offers valuable insights into the design of innovative disease treatment paradigms and alternatives to conventional drug therapy, and facilitates the clinical applications of engineering encapsulated living bacteria.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108640"},"PeriodicalIF":12.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595936","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}
Chao Zhang , Yan Liu , Tianliang Bai , Huming Shao , Ziyi Xiong , Michelle Epstein , Xin Li , Hongbing Chen
{"title":"A novel member of biomimetic nano vesicles: Functional properties and research progress of hybrid-membered nanovesicles","authors":"Chao Zhang , Yan Liu , Tianliang Bai , Huming Shao , Ziyi Xiong , Michelle Epstein , Xin Li , Hongbing Chen","doi":"10.1016/j.biotechadv.2025.108637","DOIUrl":"10.1016/j.biotechadv.2025.108637","url":null,"abstract":"<div><div>In recent years, natural Extracellular Vesicles (EVs) and Artificial NanoVesicles (ANVs) have demonstrated significant advantages in pathology detection and disease treatment due to their unique biological properties. However, both vesicles exhibit inherent limitations, such as the yield issues associated with EVs and the targeting challenges encountered by Single-Membered NanoVesicles (SMNVs). Consequently, the development of Hybrid-Membered NanoVesicles (HMNVs), which integrate the advantages of both types, may expand the application scope of nanomaterials. This review examines the preparation methods and characterization techniques for HMNVs, underscoring their advantages over the parent materials. Next, we emphasize the structural stability of HMNVs as they traverse both the gastrointestinal and blood-brain barriers, highlighting their significant implications for disease detection and therapy. Finally, we outline the challenges and prospects associated with the clinical application of HMNVs. We aim to provide valuable insights into the structural exploration of these Nano vectors and their potential functional expansion.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108637"},"PeriodicalIF":12.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574783","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}
Ting He , Bingzhao Zhuo , Xing Zhao , Shanni Li, Zhouqing Luo
{"title":"Beyond nature's clock: Accelerating genomic diversity through hypermutation","authors":"Ting He , Bingzhao Zhuo , Xing Zhao , Shanni Li, Zhouqing Luo","doi":"10.1016/j.biotechadv.2025.108638","DOIUrl":"10.1016/j.biotechadv.2025.108638","url":null,"abstract":"<div><div>Gene mutation is the primary source of genetic variation, yet natural mutation rates are insufficient to meet the demands of biotechnological applications. This review systematically examines advancements in hypermutation technologies designed to overcome this limitation, focusing on targeted, multi-target, and genome-wide approaches, and their transformative applications across diverse fields. By comparing these tools across multiple dimensions, including mutation scope, rate, and type, we provide insights to guide the selection of optimal mutagenesis tools for accessing distinct genetic landscapes and addressing practical challenges. Furthermore, we summarize the challenges that persist in this active area and highlight future directions such as developing high-throughput screening methods and AI-driven predictive models for mutational outcomes. By bridging the gap between natural mutation constraints and biotechnological needs, hypermutation technologies promise to unlock unprecedented innovations in synthetic biology, evolutionary research, and industrial applications and pave the way for exploring previously inaccessible genetic landscapes.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108638"},"PeriodicalIF":12.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564330","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}