Rahul Mahadev Shelake , Muhammad Abdullah Khalid , Jae-Yean Kim
{"title":"Microalgal bioengineering for futuristic applications in synthetic and space biology","authors":"Rahul Mahadev Shelake , Muhammad Abdullah Khalid , Jae-Yean Kim","doi":"10.1016/j.biotechadv.2025.108665","DOIUrl":"10.1016/j.biotechadv.2025.108665","url":null,"abstract":"<div><div>Extreme environmental conditions on Earth and in space pose significant challenges to sustaining life. As global population growth exacerbates issues such as climate change, food security, and resource depletion, innovative solutions are needed. Similarly, confined and isolated environments on Earth and in space lack essential life-supporting resources such as oxygen, water, and food. Combined with the challenges of microgravity and radiation exposure, these factors present substantial obstacles to advancing human space exploration. Biotechnological innovations are essential to enable long-term habitation in extraterrestrial environments. Microalgae, with their high photosynthetic efficiency, diverse metabolic capabilities, omnipresence in the natural world, and adaptability to extreme conditions, have emerged as promising candidates for synthetic biology (SynBio) applications. Recent advancements in genetic engineering, particularly CRISPR-based genome editing (GE), provide unprecedented opportunities to enhance microalgal traits for the sustainable bioproduction of oxygen, water, and nutrition in space missions. Engineered microalgae hold immense potential for bioregenerative life support systems (BLSS), supplying essential resources while reducing logistical constraints. This review examines the integration of SynBio and GE in microalgae, highlighting their role in space research and environmental sustainability. We discuss key advancements in CRISPR and innovative (omics, synthetic gene circuits, artificial cells, nanotechnology, and artificial intelligence) technologies relevant to metabolic pathway engineering and space-adapted microalgal systems, underscoring their transformative potential in addressing both terrestrial and extraterrestrial challenges.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108665"},"PeriodicalIF":12.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738156","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}
Pavan K Inguva, Saikat Mukherjee, Pierre J Walker, Vico Tenberg, Cedric Devos, Sunkyu Shin, Yanchen Wu, Srimanta Santra, Jie Wang, Shalini Singh, Mona A Kanso, Shin Hyuk Kim, Bernhardt L Trout, Martin Z Bazant, Allan S Myerson, Richard D Braatz
{"title":"Mechanistic modeling of lipid nanoparticle formation for the delivery of nucleic acid therapeutics.","authors":"Pavan K Inguva, Saikat Mukherjee, Pierre J Walker, Vico Tenberg, Cedric Devos, Sunkyu Shin, Yanchen Wu, Srimanta Santra, Jie Wang, Shalini Singh, Mona A Kanso, Shin Hyuk Kim, Bernhardt L Trout, Martin Z Bazant, Allan S Myerson, Richard D Braatz","doi":"10.1016/j.biotechadv.2025.108643","DOIUrl":"https://doi.org/10.1016/j.biotechadv.2025.108643","url":null,"abstract":"<p><p>Nucleic acids such as mRNA have emerged as a promising therapeutic modality with the capability of addressing a wide range of diseases. Lipid nanoparticles (LNPs) as a delivery platform for nucleic acids were used in the COVID-19 vaccines and have received much attention. While modern manufacturing processes which involve rapidly mixing an organic stream containing the lipids with an aqueous stream containing the nucleic acids are conceptually straightforward, detailed understanding of LNP formation and structure is still limited and scale-up can be challenging. Mathematical and computational methods are a promising avenue for deepening scientific understanding of the LNP formation process and facilitating improved process development and control. This article describes strategies for the mechanistic modeling of LNP formation, starting with strategies to estimate and predict important physicochemical properties of the various species such as diffusivities and solubilities. Subsequently, a framework is outlined for constructing mechanistic models of reactor- and particle-scale processes. Insights gained from the various models are mapped back to product quality attributes and process insights. Lastly, the use of the models to guide development of advanced process control and optimization strategies is discussed.</p>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":" ","pages":"108643"},"PeriodicalIF":12.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727743","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}
Danxia Wu , Moxian Chen , W.M.W.W. Kandegama , Guandi He , Xiangyang Li
{"title":"Susceptibility genes in plants: from molecular mechanisms to ecological implications for disease resistance","authors":"Danxia Wu , Moxian Chen , W.M.W.W. Kandegama , Guandi He , Xiangyang Li","doi":"10.1016/j.biotechadv.2025.108664","DOIUrl":"10.1016/j.biotechadv.2025.108664","url":null,"abstract":"<div><div>Susceptibility (<em>S</em>) genes serve as critical regulatory elements in plant-pathogen interactions and have been successfully targeted through genome editing approaches for disease resistance improvement in numerous crop species, achieving substantial progress across diverse agricultural systems. However, emerging evidence demonstrates that <em>S</em> genes simultaneously fulfill essential functions in plant development, physiological homeostasis, and environmental adaptation, reflecting their fundamental biological indispensability beyond pathogen susceptibility. This review synthesizes current knowledge of the functional classification, genome editing outcomes, and evolutionary significance of <em>S</em> genes, emphasizing that while targeted modification represents a powerful tool for resistance breeding, comprehensive understanding of their pleiotropic roles becomes increasingly important for optimizing breeding outcomes. We propose an integrative research framework that complements existing genome editing approaches by positioning <em>S</em> genes as dynamic regulatory interfaces within plant-environment networks, exploring complementary strategies for modulating <em>S</em> gene function through beneficial microbiome management, hormonal pathway optimization, and ecologically informed agricultural practices. This multidimensional approach may inform future crop protection strategies that integrate molecular precision with ecological sustainability.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108664"},"PeriodicalIF":12.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722427","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":"Bioactive metabolites and extracellular vesicles from the marine chlorophyte genus Tetraselmis: Review","authors":"Thomas Conlon, Nicolas Touzet","doi":"10.1016/j.biotechadv.2025.108662","DOIUrl":"10.1016/j.biotechadv.2025.108662","url":null,"abstract":"<div><div>Microalgal biotechnology offers sustainable applications that align with the principles of the circular bioeconomy, providing innovative and resource-efficient solutions to help achieve the United Nations' Sustainable Development Goals. Within this framework, the marine chlorophyte genus <em>Tetraselmis</em> is attracting increasing attention for its potential in biotechnology and biomedicine. As facultative mixotrophs, <em>Tetraselmis</em> species exhibit metabolic flexibility and high tolerance to abiotic stresses, enabling the efficient biosynthesis of a wide range of bioactive compounds, including polyunsaturated fatty acids (PUFAs), carotenoids, tocopherols, and phenolic compounds. These compounds exhibit a broad spectrum of beneficial biological activities, such as antioxidant, anti-inflammatory, immune-modulating, antibacterial, antiviral, and anticancer properties, making <em>Tetraselmis</em> species valuable resources for functional foods, nutraceuticals, cosmetics, aquaculture, and pharmaceuticals. Furthermore, potential applications have been further supported by the European Union's approval of <em>T. chuii</em> for human consumption under the novel food regulatory framework. Additionally, extracellular vesicles (EVs) derived from <em>T. chuii</em> are among the most well-characterised microalgal-derived EVs. These EVs have been shown to reduce oxidative stress, modulate inflammatory pathways, and exhibit low toxicity and high biocompatibility in both human cell lines and in vivo models. Given their natural bioactive composition, these EVs offer promising potential as an innovative platform for drug delivery. This review explores the metabolic flexibility, bioactive compound production, and the therapeutic potential of <em>Tetraselmis</em> species and their EVs, highlighting their diverse applications in biotechnology and biomedicine. The integration of emerging interdisciplinary tools such as artificial intelligence (AI) and synthetic biology presents new opportunities to optimise cultivation strategies, enhance EV yield and functionality, and enable the engineering of strain-specific traits. These advances are expected to accelerate the development of precision <em>Tetraselmis</em>-based applications across biomedicine, aquaculture, and environmental sustainability, reinforcing their potential for industrial-scale adoption within next-generation biomanufacturing platforms.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108662"},"PeriodicalIF":12.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711233","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}
Ziling Zhao , Qiyang Qu , Fuwei Sun , Jiachen Zang , Bowen Zheng , Tuo Zhang , Guanghua Zhao , Chenyan Lv , Zhongjiang Wang
{"title":"Advances of computational protein design: Principles, strategies and applications in nutrition and health","authors":"Ziling Zhao , Qiyang Qu , Fuwei Sun , Jiachen Zang , Bowen Zheng , Tuo Zhang , Guanghua Zhao , Chenyan Lv , Zhongjiang Wang","doi":"10.1016/j.biotechadv.2025.108656","DOIUrl":"10.1016/j.biotechadv.2025.108656","url":null,"abstract":"<div><div>Computational methods and AI technology have had a profound impact on protein design, significantly enhancing the ability to predict protein structures and create proteins with custom-tailored functions. With the help of computational methods, traditional protein design strategies such as directed evolution, fusion protein, and key subunit interface redesign show unprecedented progress in the design of various protein biomaterials such as nanocages, nanocarriers, antibodies, biocatalytic enzymes and inhibitory peptides. Strategies include physics-mediated design, which leverages the physical principles underlying protein structure and dynamics, and AI-mediated design, which employs machine learning techniques to generate and optimize protein configurations. Together, these approaches represent the cutting-edge methodologies in the rational design of novel proteins with desired functions. By using these approaches, novel protein molecules, assemblies, antibodies and responsive nanofibrils were constructed, which can be further applied in the field of nutrition and health.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108656"},"PeriodicalIF":12.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713454","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}
Yitie Huang, Mengying Jin, Han Gao, Xiuhui Yang, Mingqiang Xia, Ou Li
{"title":"Advances in sphingan production: Biosynthesis and synthetic biology strain modification strategies based on Sphingomonas","authors":"Yitie Huang, Mengying Jin, Han Gao, Xiuhui Yang, Mingqiang Xia, Ou Li","doi":"10.1016/j.biotechadv.2025.108659","DOIUrl":"10.1016/j.biotechadv.2025.108659","url":null,"abstract":"<div><div>The genus <em>Sphingomonas</em> represents a significant resource of microbial strains capable of synthesizing biopolymers. Many of these strains are capable of producing extracellular polysaccharides with diverse structures, including gellan, welan, and diutan, collectively referred to as sphingans. Currently, several sphingans, such as gellan and sanxan, have been produced and utilized in the food and pharmaceutical sectors. However, many more sphingans remain to be explored. This paper provides a review of the current taxonomic status of the <em>Sphingomonas</em> genus, and synthesizes the existing research on the structure, biosynthetic pathways, molecular genetics, and genetic engineering of sphingans. It also offers insights into prospective research directions for the future.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108659"},"PeriodicalIF":12.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714257","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}
Yaoyun Wu , Wei Song , Wanqing Wei , Jian Wen , Liming Liu , Jing Wu
{"title":"Enzymatic CN bond formation and cleavage reaction: Advances and perspectives","authors":"Yaoyun Wu , Wei Song , Wanqing Wei , Jian Wen , Liming Liu , Jing Wu","doi":"10.1016/j.biotechadv.2025.108661","DOIUrl":"10.1016/j.biotechadv.2025.108661","url":null,"abstract":"<div><div>Cofactor-(in)dependent enzymatic systems (CNases) play a pivotal role in catalyzing the formation and cleavage of C<img>N bonds, a critical reaction for producing a wide range of chemicals. This review provides a comprehensive analysis of the classification, structural characteristics, reaction mechanisms, and the impact of protein engineering on the performance of key enzyme groups, including ATP-dependent CNases, nicotinamide-dependent oxidoreductases, flavin adenine dinucleotide-dependent oxidoreductases, pyridoxal 5′-phosphate dependent CNases, 4-methylideneimidazole-5-one-dependent CNases, radical CNases, metallo-CNases and cofactor-independent CNases. The latest advancements in cofactor-dependent enzymatic systems for C<img>N bond formation and cleavage are summarized, with a focus on key applications. Future perspectives are also discussed regarding the potential of these enzymatic systems in establishing efficient biorefineries.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"83 ","pages":"Article 108661"},"PeriodicalIF":12.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706202","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}
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}