Shuaiqi Meng , Zhongyu Li , Peng Zhang , Yu Ji , Ulrich Schwaneberg
{"title":"Capturing intrinsic protein dynamics for explaining beneficial substitutions from protein engineering campaigns","authors":"Shuaiqi Meng , Zhongyu Li , Peng Zhang , Yu Ji , Ulrich Schwaneberg","doi":"10.1016/j.biotechadv.2025.108660","DOIUrl":"10.1016/j.biotechadv.2025.108660","url":null,"abstract":"<div><div>Directed evolution and knowledge-based design have been proven to be successful strategies for engineering proteins to desired applications. Traditional engineering strategies have focused on analyzing “hot spots” such as the substrate binding pocket to identify key positions. Yet, with a deeper understanding of protein structure-function relationships, many protein residues could significantly contribute to protein functionality, as they have the potential to influence one another and consequently alter protein conformation through the interconnected network formed by amino acids. Hence, it is essential to highlight the intrinsic dynamics in guiding protein engineering. This involves two main aspects: firstly, focusing on the exploration of protein conformation dynamics in order to understand how substitutions affect global and local conformations. Secondly, analyzing the intricate networks of amino acids in order to capture the amino acid interaction network and understand the impact of distal mutagenesis on the protein mutability landscape. Understanding intrinsic dynamics can deepen the understanding of both global and local enzyme properties, and help identify critical hotspots that researchers often overlooked in traditional protein engineering campaigns but are essential for property improvements. Additionally, we also discuss the current computational and experimental approaches in capturing protein conformations and amino acid networks.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108660"},"PeriodicalIF":12.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694675","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}
Geng Wang , Asma Abdella , Mohamadali Fakhari , Jie Dong , Kevin K. Yang , Shang-Tian Yang
{"title":"Recent advances in engineering microbial lipases for industrial applications","authors":"Geng Wang , Asma Abdella , Mohamadali Fakhari , Jie Dong , Kevin K. Yang , Shang-Tian Yang","doi":"10.1016/j.biotechadv.2025.108658","DOIUrl":"10.1016/j.biotechadv.2025.108658","url":null,"abstract":"<div><div>Lipases, a green biocatalyst found in animals, plants, and microorganisms, are widely used in the agricultural, biofuel, cosmetics, chemical, food, pharmaceutical, and textile industries due to their versatility, exceptional specificity, and ease of production and use. However, the presence of multiple isoforms of microbial lipases often limits their applications and requires costly purification. There are also growing demands for improved lipase stability, activity, and specificity in industrial applications. One emerging research direction in this field is integrating synthetic biology and engineering tools to design novel lipases for diverse industrial applications. Recent progress in protein engineering, immobilization technologies, and artificial intelligence (AI) tools have significantly improved lipase catalytic performance. This paper provides a comprehensive review of the classification, general characteristics, industrial production and applications of lipases and recent advances in engineering lipases and lipase-producing microbial cells to develop novel lipase-based bioprocesses and bioproducts.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108658"},"PeriodicalIF":12.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697571","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}
Raquel Ledo Doval , Klaas Timmermans , Ronald P. de Vries
{"title":"Marine fungal enzymes as potential degraders of the diverse seaweed cell-walls","authors":"Raquel Ledo Doval , Klaas Timmermans , Ronald P. de Vries","doi":"10.1016/j.biotechadv.2025.108653","DOIUrl":"10.1016/j.biotechadv.2025.108653","url":null,"abstract":"<div><div>Marine fungi play a critical yet understudied role in marine ecosystems, contributing to microbial diversity and ecological balance through their interactions with seaweed and other organisms. These interactions are essential for nutrient cycling and maintaining ecosystem health. While the carbohydrate-active enzymes (CAZymes) of terrestrial fungi are well-documented for plant biomass degradation, the enzymatic capabilities of marine fungi, specifically for degrading seaweed biomass, remain less explored. The distinct sugar composition of seaweed has likely shaped the CAZome of marine fungi, specifically in activities targeting seaweed cell wall polysaccharides. This review focuses on the potential of marine fungal CAZymes as biocatalysts for the degradation of seaweed cell wall polysaccharides. We provide a detailed examination of the unique sugar composition of seaweed cell walls, such as alginates, fucoidans, and carrageenans, and analyze the putative CAZy abilities of marine fungi to target these structures. A better understanding of marine fungal enzymatic processes could unlock sustainable strategies for extracting valuable compounds, such as proteins and nutraceuticals, from seaweed biomass, while enabling the comprehensive valorization of all biomass fractions within a biorefinery framework. By summarizing current knowledge and identifying research gaps, this review highlights the untapped potential of marine fungi as key agents in the development of efficient, integrated seaweed biorefineries.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108653"},"PeriodicalIF":12.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697546","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}
Li Hu , Yuqi Ye , Yuzhu Li , Xinyun Tan , Xinyu Liu , Tingran Zhang , Jingyao Wang , Zongjun Du , Mengqi Ye
{"title":"Bacteria–algae synergy in carbon sequestration: Molecular mechanisms, ecological dynamics, and biotechnological innovations","authors":"Li Hu , Yuqi Ye , Yuzhu Li , Xinyun Tan , Xinyu Liu , Tingran Zhang , Jingyao Wang , Zongjun Du , Mengqi Ye","doi":"10.1016/j.biotechadv.2025.108655","DOIUrl":"10.1016/j.biotechadv.2025.108655","url":null,"abstract":"<div><div>Rising atmospheric CO₂ levels require innovative strategies to increase carbon sequestration. Bacteria–algae interactions, as pivotal yet underexplored drivers of marine and freshwater carbon sinks, involve multiple mechanisms that amplify CO₂ fixation and long-term storage. This review systematically describes the synergistic effects of bacteria–algae consortia spanning both microalgae (e.g., <em>Chlorella vulgaris</em> and <em>Phaeodactylum tricornutum</em>) and macroalgae (e.g., <em>Macrocystis</em> and <em>Laminaria</em>) on carbon sequestration. These effects include (1) molecular-level regulation (e.g., signal transduction via <em>N</em>-acyl-homoserine lactones (AHLs), and horizontal gene transfer), (2) ecological facilitation of recalcitrant dissolved organic carbon (RDOC) formation, and (3) biotechnological applications in wastewater treatment and bioenergy production. We highlight that microbial crosstalk increases algal photosynthesis by 20–40 % and contributes to 18.9 % of kelp-derived RDOC storage. Furthermore, engineered systems integrating algal–bacterial symbiosis achieve greater than 80 % nutrient removal and a 22–35 % increase in CO₂ fixation efficiency (compared with axenic algal systems), demonstrating their dual role in climate mitigation and a circular economy. This review is the first to integrate molecular mechanisms (e.g., quorum sensing), ecological carbon transformation processes (e.g., the formation of RDOC), and applications in synthetic biology (e.g., CRISPR-engineered consortia) into a unified framework. Moreover, the novel strategy “microbial interaction network optimization” for enhancing carbon sinks is proposed. However, scalability challenges persist, including light limitations in photobioreactors and the ecological risks of synthetic consortia. By bridging microbial ecology with synthetic biology, this work provides a roadmap for harnessing bacteria–algae synergy to achieve carbon neutrality.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108655"},"PeriodicalIF":12.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697545","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}
Guangming Zhang , Jingyi Li , Shiqi Liu , Pengfei Hou , Xue Tao , Wenfang Gao , Li Sun , Longyi Lv , Jinsong Liang
{"title":"Recent advances in bioconversion of lignocellulosic biomass for volatile fatty acid production with rumen microorganisms","authors":"Guangming Zhang , Jingyi Li , Shiqi Liu , Pengfei Hou , Xue Tao , Wenfang Gao , Li Sun , Longyi Lv , Jinsong Liang","doi":"10.1016/j.biotechadv.2025.108654","DOIUrl":"10.1016/j.biotechadv.2025.108654","url":null,"abstract":"<div><div>Lignocellulosic biomass is a possible alternative for fossil fuels due to its widespread availability and numerous benefits. Volatile fatty acids (VFAs) are important intermediates that can be converted into biofuels or chemicals. VFA production from lignocellulosic biomass via anaerobic fermentation is a promising approach for resource utilization. However, the high crystallinity and complex structure of lignocellulosic biomass limit its hydrolysis, thereby affecting VFA production. Rumen microorganisms (RMs) can efficiently break down cellulose and hemicellulose, offering distinct advantages during lignocellulose degradation. Recently, RMs have been used as an efficient inoculum for degrading lignocellulosic biomass to produce VFAs. Therefore, a review of VFA production from lignocellulosic biomass via anaerobic fermentation with RMs is necessary. To date, main factors affecting VFA production, novel reactor designs for VFA production, and main strategies enhancing VFA production have not been reviewed. In this review, the key RMs, hydrolases, and metabolic pathways involved in the conversion of lignocellulose into VFAs are analyzed. Recent advancements regarding the fermentation of lignocellulose to produce VFAs by RMs and the key factors involved are summarized. Moreover, enhancement strategies for VFA production and recovery methods for VFAs are explored. Finally, the current challenges and prospects for the fermentation of lignocellulosic biomass to produce VFAs by RMs are presented. This review offers insights and approaches for efficient VFA production from lignocellulosic biomass using RMs.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108654"},"PeriodicalIF":12.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694674","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}
Xiao-Dong Pei , Dao-Quan Jiao , Zhi-Qiang Zhou , Yi-Ning He , Ge-Ge Chen , Chen Zhang , Xu-Yang Zheng , Xu Yang , Tao Wei , Cheng-Hua Wang
{"title":"Revolutionizing keratinase science: Biocatalytic advances, sustainable innovation, and industrial perspectives","authors":"Xiao-Dong Pei , Dao-Quan Jiao , Zhi-Qiang Zhou , Yi-Ning He , Ge-Ge Chen , Chen Zhang , Xu-Yang Zheng , Xu Yang , Tao Wei , Cheng-Hua Wang","doi":"10.1016/j.biotechadv.2025.108657","DOIUrl":"10.1016/j.biotechadv.2025.108657","url":null,"abstract":"<div><div>Keratinases represent a distinct class of proteolytic enzymes capable of depolymerising the highly recalcitrant structure of keratin. In recent years, these enzymes have garnered increasing attention owing to their potential applications in environmental remediation and the circular bioeconomy. This review systematically traces the historical progression of keratinase research, delineates their classification and catalytic mechanisms, and highlights their diverse application spectrum. Keratinases are broadly categorised into serine proteases, metalloproteases, and serine–metallo hybrid proteases, each exhibiting unique structural and mechanistic features. These biocatalysts have demonstrated considerable utility across agriculture, industry, biomedicine, and bioenergy sectors. The advent of protein engineering, artificial intelligence-assisted enzyme design, and synthetic biology has provided powerful tools to enhance keratinase thermostability, catalytic efficiency, and substrate specificity. Nonetheless, their widespread industrial deployment remains constrained by high production costs, suboptimal enzyme stability, and regulatory complexities. Future research should prioritize the development of multifunctional keratinase systems, integrate multi-omics approaches to elucidate keratin degradation pathways at a systems level, and foster interdisciplinary collaborations to address existing technical barriers. Collectively, this review articulates strategic directions for advancing keratinase research and paves the way for their translational applications in sustainable development and resource management.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108657"},"PeriodicalIF":12.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697572","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}
Nakia Polidori, Gianluca Catucci, Sheila J. Sadeghi, Gianfranco Gilardi
{"title":"Class A flavoprotein monooxygenases: Checkpoint and new horizons","authors":"Nakia Polidori, Gianluca Catucci, Sheila J. Sadeghi, Gianfranco Gilardi","doi":"10.1016/j.biotechadv.2025.108651","DOIUrl":"10.1016/j.biotechadv.2025.108651","url":null,"abstract":"<div><div>Flavoprotein monooxygenases (FPMOs) form a broad superfamily of enzymes that catalyze the oxyfunctionalization of a wide range of substrates, playing a crucial role in biocatalysis and sustainable chemistry. Among them, Class A enzymes are the most extensively studied, with well-established knowledge of their reaction mechanisms, stereoselectivity, and substrate scope. However, the full potential of this enzyme class remains largely untapped, as many valuable catalysts have yet to be identified and characterized. In this review, we employ a structural biology approach to provide an up-to-date overview of current knowledge on class A FPMOs. We first discuss the overall structure and catalytic mechanism. Then we present a systematic overview of all the known enzymes categorizing them biochemically as either prototypical or atypical and illustrating how similar protein scaffolds can give rise to markedly different reactions. Subsequently we discuss the co-factor preference and the protein engineering approaches. Finally, we explore uncharted areas of this field offering a strategy for discovering new catalysts.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108651"},"PeriodicalIF":12.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688796","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}
Vu Khac Hoang Bui , Le Gia Trung , Ha Huu Do , Nguyen Tien Tran , Minh Kim Nguyen
{"title":"Unlocking the algae toolbox: Cutting-edge tools for environmental and biotechnological solutions","authors":"Vu Khac Hoang Bui , Le Gia Trung , Ha Huu Do , Nguyen Tien Tran , Minh Kim Nguyen","doi":"10.1016/j.biotechadv.2025.108652","DOIUrl":"10.1016/j.biotechadv.2025.108652","url":null,"abstract":"<div><div>Algae are highly adaptable photosynthetic organisms with growing relevance in biotechnology, environmental management, and sustainable industries. Recent advancements have expanded the “Algae Toolbox”, integrating cutting-edge screening, monitoring, characterization, and large-scale production technologies. This current work critically examines the latest developments in algal research, including CRISPR-Cas9 genetic engineering, high-throughput omics, machine learning-driven modeling, and remote sensing-based ecosystem monitoring. Moreover, innovations in optical sensors, flow cytometry, biosensors, and environmental DNA have further improved precision in tracking algal dynamics. These advances support industrial scale-up, boosting productivity and sustainability in biofuels, pharmaceuticals, aquaculture, and bioremediation. However, large-scale production still faces challenges in economic viability and environmental sustainability. Future research must incorporate artificial intelligence, internet of things-enabled sensing, and synthetic biology for optimized cultivation and bioproduct harvesting. This review provides a comprehensive overview of emerging tools and methodologies, emphasizing their role in advancing algal biotechnology and global sustainability.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108652"},"PeriodicalIF":12.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688797","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}
Yue Zheng , Qiuyi Zhu , Xiaoran Li , Tongxin Ge , Shaoyun Wang , Renbing Jia , Ludi Yang , Yefei Wang , Ai Zhuang
{"title":"Epigenetic reprogramming holds promise in enhancing anti-tumor efficacy of CAR T cell therapy","authors":"Yue Zheng , Qiuyi Zhu , Xiaoran Li , Tongxin Ge , Shaoyun Wang , Renbing Jia , Ludi Yang , Yefei Wang , Ai Zhuang","doi":"10.1016/j.biotechadv.2025.108649","DOIUrl":"10.1016/j.biotechadv.2025.108649","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has emerged as a pivotal treatment modality for advanced hematological malignancies. However, clinical evidence suggests that CAR T cell therapy has a low response rate, poor efficacy for solid tumor, and a high complication rate. Recent research highlighted the crucial role of epigenetics in tumor immunity, particularly in modulating the fate and function of T cells. The epigenetic landscapes among T cell subpopulations show substantial differences, which in turn have a profound impact on the effector function and persistence of T cells. Epigenetic reprogramming holds promise for enhancing the persistence of CAR T cells, augmenting T cell infiltration, and ameliorating the immunosuppressive microenvironment while impeding immune evasion. In addition, biomarkers derived from the epigenetics serve as indicators to predict patient prognosis. In recent years, a growing number of clinical trials have been initiated to explore the combination of epigenetic drugs with CAR T cell therapy, highlighting the therapeutic promise of this synergistic approach in improving efficacy and overcome therapeutic resistance. However, the non-specificity of epigenetic drugs, side effects of epigenetic gene editing, poor efficacy in solid tumors, and instability of epigenetic biomarkers for predicting prognosis remain areas for further exploration. In this review, we explored the characterization of epigenetic modification landscapes across CAR T cell subpopulations, discussed how epigenetic reprogramming addresses challenges associated with CAR T cell therapy, and provided insights into the limitations of combining epigenetic strategies with CAR T cell therapy.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108649"},"PeriodicalIF":12.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665113","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}
Lin Cheng , Peibo Zhu , Hongjiao Ke , Shengwei Hou , Quan Luo , Xuefeng Lu
{"title":"Metabolic versatility of Marinobacter and its biotechnological potential","authors":"Lin Cheng , Peibo Zhu , Hongjiao Ke , Shengwei Hou , Quan Luo , Xuefeng Lu","doi":"10.1016/j.biotechadv.2025.108650","DOIUrl":"10.1016/j.biotechadv.2025.108650","url":null,"abstract":"<div><div>Bacteria belonging to the genus <em>Marinobacter</em> are Gram-negative, halotolerant or halophilic microorganisms. They are widely found in diverse marine and saline environments. These bacteria play crucial roles in the biogeochemical cycling of substances and energy in the global ocean. Along with their frequent interactions with other coexisting microorganisms, <em>Marinobacter</em> species have developed versatile metabolic capabilities, such as hydrocarbon degradation, biological denitrification, assimilation of metal(loid)s, and the synthesis of diverse bioactive compounds. Due to the outstanding adaptability to certain harsh environments, especially high salinity, and remarkable metabolic versatility, this genus has exhibited great potential in wastewater treatment, bioremediation, and bioproduction, and thus attracted increasing research interest from both academia and industry. The increasing number of sequenced <em>Marinobacter</em> genomes and the advancement of genetic manipulability have set a solid foundation for deepening the understanding of their ecological roles and driving the development of relevant biotechnological applications. However, practical applications are rare, and the current understanding on the genetic, biochemical, and structural bases of these metabolic processes remains still quite limited. With the further elucidation of the fundamental mechanisms of metabolic versatility, the applied research on the genus <em>Marinobacter</em> is expected to be considerably promoted in the future.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108650"},"PeriodicalIF":12.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667001","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}