Biotechnology advances最新文献

{"title":"Genetic engineering of Saccharomyces boulardii: Tools, strategies and advances for enhanced probiotic and therapeutic applications","authors":"João Paulo Carvalho ,&nbsp;David Sáez Moreno ,&nbsp;Lucília Domingues","doi":"10.1016/j.biotechadv.2025.108663","DOIUrl":"10.1016/j.biotechadv.2025.108663","url":null,"abstract":"<div><div><em>Saccharomyces boulardii</em> is a probiotic yeast that has been extensively studied in clinical trials, and it is used to treat several gut disorders. Its high survivability and the ability of secreting recombinant proteins, make <em>S. boulardii</em> an attractive delivery vessel for molecules of interest in the gut. Despite its natural mechanisms of action still not being fully understood, genetic engineering offers the advantage of rationally design the delivery of molecules of interest to the gut. As a yeast, <em>S. boulardii</em> can produce complex proteins with post translational modifications, an advantage when compared with bacterial probiotics. In addition, antibiotics can be co-administered with this yeast, increasing gut residence times and improving the positive effects on human health.</div><div>This review aims to cover the genetic engineering advances and applications of genetically engineered <em>S. boulardii</em>. The similarity of this yeast with <em>S. cerevisiae</em> has made it possible to develop tools like CRISPR-Cas9, plasmid expression systems and gene integration techniques that have allowed the modification of <em>S. boulardii</em>. These genetic tools and modifications are discussed in detail according to the state of the art highlighting the most effective ones. Genetic engineering has increased the possible applications of <em>S. boulardii,</em> including immune response modulation, enhanced pathogen neutralization, anti-obesity strategies, vitamin production. Others have used these tools to tackle its limitations as probiotic compared to others commonly used such as lactic acid bacteria, increasing its residence times and allowing the development of biocontainment strategies. Current limitations and future directions of the field such as scalability, standardization and the lack of clinical data are also highlighted and discussed.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108663"},"PeriodicalIF":12.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749207","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":"The path to biotechnological singularity: Current breakthroughs and outlook","authors":"Zhihao Wen ,&nbsp;Damin Yang ,&nbsp;Yan Yang ,&nbsp;Jingyu Hu ,&nbsp;Anna Parviainen ,&nbsp;Xin Chen ,&nbsp;Qiuhui Li ,&nbsp;Elizabeth VanDeusen ,&nbsp;Jingzhi Ma ,&nbsp;Franklin Tay","doi":"10.1016/j.biotechadv.2025.108667","DOIUrl":"10.1016/j.biotechadv.2025.108667","url":null,"abstract":"<div><div>Fueled by rapid advances in gene editing, synthetic biology, artificial intelligence, regenerative medicine, and brain-computer interfaces, biotechnology is approaching a transformative era often referred to as biotechnological singularity. CRISPR-based gene editing has revolutionized genetic engineering, enabling precise modifications for treating hereditary diseases and cancer. Synthetic biology facilitates sustainable biomaterial production and innovative therapeutic applications. Artificial intelligence accelerates drug discovery, enhances diagnostic accuracy, and personalizes treatment through deep learning models. Driven by stem cell research, regenerative medicine offers promising avenues for reversing aging and treating degenerative diseases. Brain-computer interfaces merge human cognition with technology, enabling direct neural control of prosthetics and expanding human-machine interactions. These breakthroughs, however, raise ethical, regulatory, and societal concerns, including equitable access, biosecurity risks, and the implications of human enhancement. The convergence of biological and computational technologies challenges traditional boundaries, necessitating comprehensive governance frameworks. By embracing responsible innovation, society can harness these advancements for transformative health interventions, environmental sustainability, and extended longevity. The realization of biotechnological singularity depends on interdisciplinary collaboration among scientists, policymakers, and the public to ensure that progress aligns with the well-being of humanity and ethical considerations.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108667"},"PeriodicalIF":12.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749206","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":"Haloferax and the Haloferacaceae: Potential role in bioindustry","authors":"Dana B. Griffiths ,&nbsp;Ravi P. Tiwari ,&nbsp;Daniel V. Murphy ,&nbsp;Colin Scott","doi":"10.1016/j.biotechadv.2025.108666","DOIUrl":"10.1016/j.biotechadv.2025.108666","url":null,"abstract":"<div><div>Members of the <em>Haloferacaceae</em>, a family of extremely halophilic archaea, exhibit unique physiological and genetic traits that make them promising candidates for biotechnological applications. These organisms thrive in hypersaline environments and tolerate a wide range of stresses, including high temperatures, UV radiation, and toxic metals. Their ability to grow on agro-industrial waste, coupled with their inherent resistance to contamination and the simplicity of downstream processing via osmotic shock, makes them ideal for sustainable bioproduction. Species such as <em>Haloferax mediterranei</em> have been explored for the biosynthesis of polyhydroxyalkanoates, carotenoids, halocins, and enzymes functional under extreme conditions. Species of <em>Haloferacaceae</em> can also bioremediate saline environments contaminated with hydrocarbons, heavy metals, and nitrogenous waste. Advances in genetic tools, including CRISPR interference, inducible promoters, and knock-in/knock-out systems, particularly in <em>H. volcanii</em>, have significantly expanded the engineering potential of these archaea. However, there remains a need for further innovation in genetic tools for this family. This review highlights the expanding potential of the <em>Haloferacaceae</em> for circular bioeconomy applications and identifies key technological gaps limiting their broader industrial adoption.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108666"},"PeriodicalIF":12.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759055","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":"Microalgal bioengineering for futuristic applications in synthetic and space biology","authors":"Rahul Mahadev Shelake ,&nbsp;Muhammad Abdullah Khalid ,&nbsp;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}

{"title":"Mechanistic modeling of lipid nanoparticle formation for the delivery of nucleic acid therapeutics","authors":"Pavan K. Inguva ,&nbsp;Saikat Mukherjee ,&nbsp;Pierre J. Walker ,&nbsp;Vico Tenberg ,&nbsp;Cedric Devos ,&nbsp;Sunkyu Shin ,&nbsp;Yanchen Wu ,&nbsp;Srimanta Santra ,&nbsp;Jie Wang ,&nbsp;Shalini Singh ,&nbsp;Mona A. Kanso ,&nbsp;Shin Hyuk Kim ,&nbsp;Bernhardt L. Trout ,&nbsp;Martin Z. Bazant ,&nbsp;Allan S. Myerson ,&nbsp;Richard D. Braatz","doi":"10.1016/j.biotechadv.2025.108643","DOIUrl":"10.1016/j.biotechadv.2025.108643","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 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}

{"title":"Susceptibility genes in plants: from molecular mechanisms to ecological implications for disease resistance","authors":"Danxia Wu ,&nbsp;Moxian Chen ,&nbsp;W.M.W.W. Kandegama ,&nbsp;Guandi He ,&nbsp;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,&nbsp;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}

{"title":"Advances of computational protein design: Principles, strategies and applications in nutrition and health","authors":"Ziling Zhao ,&nbsp;Qiyang Qu ,&nbsp;Fuwei Sun ,&nbsp;Jiachen Zang ,&nbsp;Bowen Zheng ,&nbsp;Tuo Zhang ,&nbsp;Guanghua Zhao ,&nbsp;Chenyan Lv ,&nbsp;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}

{"title":"Advances in sphingan production: Biosynthesis and synthetic biology strain modification strategies based on Sphingomonas","authors":"Yitie Huang,&nbsp;Mengying Jin,&nbsp;Han Gao,&nbsp;Xiuhui Yang,&nbsp;Mingqiang Xia,&nbsp;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}

{"title":"Enzymatic CN bond formation and cleavage reaction: Advances and perspectives","authors":"Yaoyun Wu ,&nbsp;Wei Song ,&nbsp;Wanqing Wei ,&nbsp;Jian Wen ,&nbsp;Liming Liu ,&nbsp;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}