Biotechnology advances最新文献

{"title":"Benzylisoquinoline alkaloid production: Moving from crop farming to chemical and biosynthesis","authors":"L. Leibetseder ,&nbsp;J. Bindics ,&nbsp;J.F. Buyel","doi":"10.1016/j.biotechadv.2025.108700","DOIUrl":"10.1016/j.biotechadv.2025.108700","url":null,"abstract":"<div><div>Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant secondary metabolites that play a key role as analgesics, anti-cancer, and anti-microbial medication. BIAs are currently exclusively produced through crop farming which adversely affects the supply chain resilience of BIA-based medication because availability is limited by low accumulation in plants and harvest seasons. Also, yields fluctuate due to annual weather changes and decrease overall due to global climate change impact on agriculture. Here we review the potential of chemical synthesis, synthetic microbial pathways and genetically engineered plants (cell- and tissue culture) as alternative BIA production approaches. The challenges and opportunities to achieve economically viable BIA titers in the gram per liter range are highlighted. Chemical BIA synthesis is robust and predictable, but yields are often &lt;30% due to the complex chemical structures and the necessary asymmetric synthesis. Synthetic microbial pathways can be engineered into heterologous production hosts like <em>Escherichia coli</em> and <em>Saccharomyces cerevisiae</em>. Whereas the former produces amino acid precursors at high titers, it fails to provide active cytochrome P450 enzymes necessary for BIA synthesis. Yeasts enable the expression of full biosynthetic pathways but struggle with relevant product titers (often &lt;10 mg L^-1). Alternatively, genetic engineering can activate the endogenous BIA pathway for a given alkaloid in the native host plant or cell cultures thereof, but currently lacks selectivity of activation and scalability of the processes. Overcoming current barriers to competitiveness will require future research to build upon the works summarized in this review.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"85 ","pages":"Article 108700"},"PeriodicalIF":12.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999511","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 on the biosynthesis of ergothioneine using microbial chassis","authors":"Xiyue Kang ,&nbsp;Peng Wu ,&nbsp;Zhenlin Han ,&nbsp;Wei Luo","doi":"10.1016/j.biotechadv.2025.108701","DOIUrl":"10.1016/j.biotechadv.2025.108701","url":null,"abstract":"<div><div>Ergothioneine (ERG) is a naturally occurring sulfur-containing amino acid with a unique structure. Due to its potent antioxidant properties and diverse biological functions, ERG has attracted increasing attention from researchers and is now widely used in the food, cosmetics, and pharmaceutical industries. The primary methods for obtaining ergothioneine include biological extraction, chemical synthesis, and biosynthesis. In recent years, biosynthesis has emerged as a promising production method for ergothioneine due to its environmental friendliness, low cost, and high safety. With the surging market demand for ergothioneine, there is an urgent need to develop metabolically engineered strains with high genetic stability, product concentration, and substrate utilization with low by-product formation. The discovery of native ergothioneine-producing strains and the construction of engineered strains using metabolic engineering techniques have become hot research topics. This review introduces the discovery process and applications of ergothioneine, summarizes its potential applications as an antioxidant, detoxifying agent, and neuroprotective agent in various industries, compares different production methods of ergothioneine, and focuses on the construction of engineered strains in different chassis strains. It also elucidates the research progress of various engineering strategies for the biosynthesis of ergothioneine, providing ideas and directions for its industrial production.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"85 ","pages":"Article 108701"},"PeriodicalIF":12.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991474","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":"Towards syngas biorefineries: The potential of microbial consortia for syngas valorisation","authors":"Silvia García-Casado ,&nbsp;Raúl Muñoz ,&nbsp;Raquel Lebrero","doi":"10.1016/j.biotechadv.2025.108699","DOIUrl":"10.1016/j.biotechadv.2025.108699","url":null,"abstract":"<div><div>Gasification has emerged as a promising platform to cope with recalcitrant organic waste within the framework of biomass-based biorefineries, producing syngas that can be fermented into valuable bioproducts. Despite its potential, syngas fermentation is based predominantly on pure cultures, which faces significant challenges, including the limited portfolio of generated compounds (primarily acetate and ethanol) and their low productivity. To address these bottlenecks, the potential of microbial consortia as effective platforms for syngas conversion has been evaluated. Syngas biomethanation using mixed cultures is a well-established process, with pilot-scale implementations yielding promising results. Alternatively, the production of carboxylic acids has emerged as an interesting option compared to pure cultures, as comparable acetate productivities can be achieved along with the possibility for chain elongation to butyrate or caproate. However, the feasibility of using mixed cultures to produce alcohols and other high-value compounds from syngas remains underexplored. Advancing the field will also require the development of innovative technologies to overcome inherent barriers and fully unlock the potential of syngas-based bioprocesses. Key challenges include the presence of impurities and variability in syngas composition, mass transfer limitations in bioreactors, and the need for efficient downstream effluent purification. In this context, mixed cultures emerge as a robust approach capable of buffering syngas fluctuations and tolerating certain impurities. At the same time, the development of novel gas phase bioreactors and innovative membrane-based systems for effluent purification is crucial for enhancing CO and H₂ mass transfer and improving products titers, respectively.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"85 ","pages":"Article 108699"},"PeriodicalIF":12.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941427","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":"Machine learning in predictive biocatalysis: A comparative review of methods and applications","authors":"Neha Tripathi ,&nbsp;Joan Hérisson ,&nbsp;Jean-Loup Faulon","doi":"10.1016/j.biotechadv.2025.108698","DOIUrl":"10.1016/j.biotechadv.2025.108698","url":null,"abstract":"<div><div>In recent years, machine learning has significantly advanced predictive biocatalysis, enabling innovative approaches to enzyme function prediction, biocatalyst discovery, reaction modeling, and metabolic pathway optimization. This review provides a comparative analysis of current methodologies, highlighting the intersection between computational tools and biochemical data for predictive biocatalysis applications. Key aspects covered include enzyme classification, reaction annotation, enzyme-substrate specificity, reaction outcomes, and kinetic parameter prediction. We discuss various machine learning approaches, such as neural networks with increased depth, convolutional networks, graph-based architectures, and transformer models, highlighting their respective strengths and limitations. The integration of large-scale data, representation and featurization techniques, and robust validation methods has accelerated enzyme discovery and the development of eco-friendly, sustainable biocatalytic processes. In the future, machine learning is anticipated to play a central role in connecting computational insights with practical enzyme engineering efforts, advancing applications in synthetic biology, metabolic engineering, and green biocatalysis.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108698"},"PeriodicalIF":12.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916384","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":"Multigene engineering in plants: Technologies, applications, and future prospects","authors":"Ruchika Rajput ,&nbsp;Brandon A. Boone ,&nbsp;Rushil Mandlik ,&nbsp;Md Torikul Islam ,&nbsp;Yiping Qi ,&nbsp;Jack Wang ,&nbsp;Rodolphe Barrangou ,&nbsp;Rosangela Sozzani ,&nbsp;Carrie A. Eckert ,&nbsp;Gerald A. Tuskan ,&nbsp;Jin-Gui Chen ,&nbsp;Xiaohan Yang","doi":"10.1016/j.biotechadv.2025.108697","DOIUrl":"10.1016/j.biotechadv.2025.108697","url":null,"abstract":"<div><div>The emerging bioeconomy presents a promising solution to both economic and environmental challenges. Within the bioeconomy, plants serve as a renewable, sustainable, and cost-effective source of foods, fuels, chemicals, and materials. However, traditional breeding and single-gene engineering approaches fall short in addressing complex traits (e.g., drought tolerance, disease resistance, yield, nutrient use efficiency) which are controlled by multiple genes. The complexity of plant biology often necessitates the use of multigene engineering (MGE), which involves simultaneous ectopic expression, up/down-regulation, or editing of multiple genes, to enhance plant traits relevant to the bioeconomy. These genes may be associated with distinct traits or function as components of specific metabolic and regulatory pathways. This review summarizes current technologies for MGE within the synthetic biology-driven Design-Build-Test-Learn (DBTL) framework, detailing its four key stages: Design – gene construct development; Build – DNA assembly and plant transformation; Test – the molecular, biochemical, and physiological characterization of engineered plants; and Learn – computational modeling to refine, multiplex and iterate the process. Despite good progress in the applications of MGE in biofortification, metabolic engineering, and stress resilience, challenges remain in construct stability, coordinated gene expression, and regulatory predictability. We identified optimization paths and future directions to accelerate MGE deployment in sustainable agriculture, with possible societal benefits including reduced production costs, increased yield, and improved food and nutritional security.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"85 ","pages":"Article 108697"},"PeriodicalIF":12.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941442","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":"Chemical imaging of lignocellulosic biomass: Mapping plant chemistry","authors":"Noah Remy ,&nbsp;David Touboul ,&nbsp;Edith Nicol ,&nbsp;Séverine Humbert ,&nbsp;Luminita Duma ,&nbsp;Pedro Lameiras ,&nbsp;Jean-Hugues Renault ,&nbsp;Gabriel Paës","doi":"10.1016/j.biotechadv.2025.108696","DOIUrl":"10.1016/j.biotechadv.2025.108696","url":null,"abstract":"<div><div>Lignocellulosic biomass (LB), which encompasses various plant samples, requires thorough characterization to optimize its use as a carbon resource. Chemical imaging simultaneously provides chemical and spatial information, offering significant benefits for LB analysis. This review presents an overview of the most advanced techniques for achieving this goal. By combining spectrometry and microscopy, microspectroscopy enables chemical imaging using various irradiation sources (IR, Raman, fluorescence, among others), allowing for the quantitative mapping of key LB components such as lignins, cellulose, and hemicelluloses. Mass Spectrometry Imaging (MSI) generates a mass spectrum for each spot of a sample thereby creating a chemical image pixel-by-pixel. MSI techniques like Matrix-Assisted Laser Desorption/Ionization (MALDI), down to 2–5 μm spatial resolution, and Secondary Ion Mass Spectrometry (SIMS), down to 300 nm for molecular analysis, effectively map small molecules in LB. In contrast, Desorption ElectroSpray Ionization (DESI) has been applied to plant extracts but remains largely unexplored for LB applications. Nuclear Magnetic Resonance (NMR) provides insight into various LB properties too. Solid-state NMR (ssNMR) and Dynamic Nuclear Polarization (DNP) help elucidate the structure of LB, sometimes aided by 3D atomistic modeling, whereas micro–Magnetic Resonance Imaging (micro-MRI) and Time-Domain (TD-NMR) probe the impact of water on LB properties.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"85 ","pages":"Article 108696"},"PeriodicalIF":12.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941396","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":"Why the military should be interested in biomedical technology: four domains of innovation that could change fighting power","authors":"David Gisselsson ,&nbsp;Jean-Paul Pirnay ,&nbsp;Michael Wiederoder ,&nbsp;Corey Hart ,&nbsp;Alberto Rinaldi ,&nbsp;Olivier Gorgé ,&nbsp;Heather Iriye ,&nbsp;Luís Carvalho ,&nbsp;Lucie Sedlackova ,&nbsp;Øyvind Voie ,&nbsp;Yohan Robinson","doi":"10.1016/j.biotechadv.2025.108695","DOIUrl":"10.1016/j.biotechadv.2025.108695","url":null,"abstract":"<div><div>Biotechnology is a rapidly progressive field, currently transforming agriculture, healthcare, and life sciences. This rapid development comes with serious legal and ethical challenges as well as risks for human security and health. NATO has prioritized biotechnology and human enhancement technologies for defense, focusing on legitimate, defensive applications. This paper highlights four clusters of biomedical technologies with the potential to enhance warfighter performance:<ul><li><span>1.</span><span><div><strong>Small-scale sensors with response capability</strong>: These sensors, already used in civilian healthcare for glucose monitoring and insulin dosing, could be adapted for military use to administer antidotes or antibiotics in response to chemical or biological threats.</div></span></li><li><span>2.</span><span><div><strong>Microbial engineering:</strong> Tailor-made probiotics could prepare soldiers' gut microbiomes to prevent travel-related illnesses, while bacteriophages, can be used to combat infections resistant to antibiotics.</div></span></li><li><span>3.</span><span><div><strong>Human-machine interaction</strong>: Neurocybernetics is transforming military robotics by enabling seamless communication between humans and machines.</div></span></li><li><span>4.</span><span><div><strong>Omics and informatics</strong>: Precision medicine combined with machine intelligence can be used for medical screening and monitoring of soldiers, as well as for biomedical intelligence gathering.</div></span></li></ul></div><div>These technologies, progressing in civilian sectors, have significant potential to enhance military capabilities in the near future (5–10 years). Oversight and prioritization of human rights are essential to ensure responsible application, maintaining human dignity, bodily integrity, and personal autonomy even in wartime. As military innovation systems worldwide are advancing in strategic biotechnologies, it is critical for NATO countries to maintain synergistic intra-alliance collaboration in this intense field.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108695"},"PeriodicalIF":12.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919811","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":"Emerging research insights and future perspectives on the advancement of eccDNA: A comprehensive review","authors":"Kunlong Qi ,&nbsp;Zheliang Liu ,&nbsp;Felix Kwame Amevor ,&nbsp;Dan Xu ,&nbsp;Wei Zhu ,&nbsp;Tong Li ,&nbsp;Yingjie Wang ,&nbsp;Liuting Wu ,&nbsp;Gang Shu ,&nbsp;Xiaoling Zhao","doi":"10.1016/j.biotechadv.2025.108693","DOIUrl":"10.1016/j.biotechadv.2025.108693","url":null,"abstract":"<div><div>Extrachromosomal circular DNA (eccDNA) is a class of chromosome-independent circular DNA molecules found in diverse organisms, including plants, animals, and microorganisms. Recent research has highlighted its roles in gene regulation, genome stability, and disease pathogenesis, with growing recognition of eccDNA as a valuable biomarker for cancer diagnosis, prognosis, and monitoring in precision medicine. Studies have also linked eccDNA to non-neoplastic diseases and normal tissue biology, broadening its biological significance beyond malignancies. Technological advancements have greatly enhanced the detection and characterization of eccDNA, enabling a better understanding of its formation, diversity, and functions. In agriculture, eccDNA research has shown potential applications for improving livestock productivity and health management. This review provides a comprehensive analysis of the current state of eccDNA research, focusing on its formation mechanisms, classification, biological functions, and implications in both disease and agriculture. Despite significant progress, challenges remain in fully understanding the biological roles, formation processes, and practical applications of eccDNA. Future research should adopt interdisciplinary approaches that integrate genomics, bioinformatics, and material science to further elucidate the complexities of eccDNA. By advancing our knowledge of eccDNA, researchers may unlock novel diagnostic, therapeutic, and biotechnological innovations, particularly in cancer treatment and livestock breeding programs.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108693"},"PeriodicalIF":12.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893127","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 stressing point: how plants respond to environmental stimuli","authors":"Raymond Joseph ,&nbsp;Wilgince Apollon ,&nbsp;Antonio Costa De Oliveira","doi":"10.1016/j.biotechadv.2025.108691","DOIUrl":"10.1016/j.biotechadv.2025.108691","url":null,"abstract":"<div><div>This review article examines how environmental stress affects plant development by changing their morphological features, physiological processes, biochemical pathways, and gene regulatory mechanisms. Eukaryotic plants face major agricultural challenges because they are stationary, making them constantly susceptible to adverse conditions such as drought, salinity, extreme temperatures, and heavy metal contamination. Key findings highlight the genetic and molecular factors that drive adaptive responses, including the production of osmoprotective and antioxidant compounds that improve stress tolerance. For instance, the review shows how wheat produces proline during water stress and discusses the role of differentially expressed genes (DEGs) in maize. It also covers how salt stress responses are regulated by Dehydration-Responsive Element-Binding (DREB) and basic/helix-loop-helix (bHLH) transcription factors, as well as how gene expression in sugar beet is controlled by non-coding RNAs. Furthermore, we examine how plants adapt to thermal and light stress, describing physiological and biochemical changes, including the regulation of heat shock proteins and gene expression under intense light conditions. Overall, our review emphasizes that plant stress adaptation relies on complex genetic, physiological, and biochemical mechanisms that support the development of resilient crop varieties and sustainable farming practices.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108691"},"PeriodicalIF":12.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering plant hosts for high-efficiency accumulation of flavonoids: Advances, challenges and perspectives","authors":"Yameng Xu ,&nbsp;Xiaoyang Ge ,&nbsp;Yongkun Lv ,&nbsp;Zhaoen Yang ,&nbsp;Fuguang Li ,&nbsp;Zuoren Yang","doi":"10.1016/j.biotechadv.2025.108692","DOIUrl":"10.1016/j.biotechadv.2025.108692","url":null,"abstract":"<div><div>Flavonoids are a vital class of compounds that contribute to plant resistance and also beneficial to human health. Increasing plant flavonoid content or enabling the synthesis of specific flavonoids can enhance plant resistance to biotic and abiotic stress while augmenting their nutritional value, thereby supporting sustainable agricultural practices. Although numerous studies have focused on increasing flavonoid content in plants, traditional engineering strategies lack the precision required to selectively regulate the synthesis of individual flavonoids. In contrast, systems and synthetic biology provide innovation approaches to address these challenges. Here, we summarize research on the distribution, biosynthetic pathways, and transcriptional regulation of flavonoids in plants. Subsequently, we analyze current progress in altering plant-flavonoid content, including transcriptional regulation, transporter engineering, and lifting rate-limiting steps. Additionally, we summarize potential strategies for precisely altering flavonoid biosynthetic pathways, including the selection of ideal hosts, designating artificially modifiable genetic elements, accelerating enzyme evolution by protein engineering, enhancing cascade biocatalysis and metabolic flux, and rebalancing metabolic fluxes. Finally, we discuss current limitations and prospects for building a next-generation plant hosts for high-efficiency flavonoid biosynthesis. This review aims to provide theoretical guidance for the modification and reconstruction of flavonoid biosynthesis in plants using systems and synthetic biology approaches.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":"84 ","pages":"Article 108692"},"PeriodicalIF":12.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900576","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}