生物设计研究(英文)最新文献

{"title":"Recent advances in AI-driven deep eutectic solvent design for biocatalysis: Co-design of extremozyme and reaction medium.","authors":"Yuxuan Hou, Jinyu Meng, Binghui Chen, Jifeng Yuan, Shizhen Wang","doi":"10.1016/j.bidere.2026.100109","DOIUrl":"https://doi.org/10.1016/j.bidere.2026.100109","url":null,"abstract":"<p><p>Deep eutectic solvents (DES) have emerged as sustainable, highly tunable alternatives to conventional organic media for non-aqueous biocatalysis. DES dynamically interact with enzymes to shift reaction equilibria, enhance thermostability and tailor stereoselectivity. However, the vast combinatorial space and complex physicochemical properties of DES make traditional trial-and-error solvent engineering highly inefficient. This review systematically examines recent advancements in DES-driven biocatalysis and highlights the role of artificial intelligence (AI) for rational DES design. Specifically, it synthesizes evidence that DES composition and water content jointly shape enzyme-specific microenvironments and thereby affect catalytic performance. Extremozymes are also evaluated as candidate catalysts for DES-containing media and as sources of potentially transferable adaptation features for enzyme engineering. It then discusses how AI can support DES formation screening, prediction of physicochemical properties using quantitative structure-property relationship (QSPR) models, and candidate formulation generation at the solvent level. At the system level, the focus shifts to predicting how a specific enzyme responds to a defined formulation in terms of activity and stability. Finally, we outline a mechanistically informed, multi-objective framework that integrates DES composition, enzyme sequence and structure, and operating conditions with physicochemical calculations, AI-based prediction, and experimental validation, providing a practical route toward genuine DES-enzyme co-design.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 3","pages":"100109"},"PeriodicalIF":7.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breeding of <i>Serratia marcescens</i> GEN-M54 for high prodigiosin yield via two-step light fermentation.","authors":"Jingxiang Sun, Yongxiang Cui, Feng Guo, Yujia Jiang, Wenming Zhang, Wankui Jiang, Fengxue Xin, Min Jiang","doi":"10.1016/j.bidere.2026.100110","DOIUrl":"https://doi.org/10.1016/j.bidere.2026.100110","url":null,"abstract":"<p><p>Prodigiosin is a tripyrrole-based microbial pigment that exhibits diverse biological activities, including antioxidant, antimicrobial, and anticancer properties. Moreover, it possesses excellent color fastness and dye uptake, making it a promising candidate in medicine, cosmetics and dye industries. In this study, the high-prodigiosin-producing mutant <i>Serratia marcescens</i> strain GEN-M54 was obtained through sequential physical and chemical mutagenesis. The effect of light on the prodigiosin production was investigated, and a two-step sequential light fermentation strategy was developed to promote the prodigiosin accumulation. Additionally, gene transcription analysis was conducted to elucidate changes in the metabolic flux of prodigiosin precursor synthesis under red-light stress conditions. Finally, a prodigiosin production of 6623.1 mg/L and a content of 471.4 mg/g were achieved through the two-step fermentation strategy, representing an increase of 77.1% and 46.8%, respectively. Overall, this study provides an efficient microbial platform and an efficient fermentation strategy for future prodigiosin production.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 3","pages":"100110"},"PeriodicalIF":7.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of Rumen microbes utilizing lignocellulose for high-value chemical production.","authors":"Jinna Cui, Feng Li, Qingsheng Qi, Peiyong Qin, Xiaoming Su, Hongdong Quan, Dian Wang, Xiaoni Chen, Jian Zhang, Zhanying Liu","doi":"10.1016/j.bidere.2026.100107","DOIUrl":"https://doi.org/10.1016/j.bidere.2026.100107","url":null,"abstract":"<p><p>Lignocellulose is the most abundant renewable carbon resource in nature. However, its structural recalcitrance, arising from the complex association of cellulose, hemicellulose, and lignin, results in high pretreatment costs and inefficient enzymatic hydrolysis, thereby limiting its high-value utilization. The rumen harbors a diverse anaerobic microbial community with efficient lignocellulose-degrading capacity, interconnected metabolic networks, and considerable functional adaptability, making the rumen microbiome a promising biological platform for lignocellulose conversion. This review systematically summarizes the mechanisms of lignocellulose degradation by rumen microorganisms, the metabolic pathways underlying value-added chemical production, and the process-, community-, and genetic-level strategies used to improve lignocellulose conversion performance. It further discusses major constraints on the development of rumen-derived bioconversion systems, including the instability of <i>in vitro</i> microbial communities, limited control over metabolic flux, and difficulties in process scale-up. Finally, the potential of multi-omics analyses and synthetic biology to improve community stability, metabolic controllability, and product selectivity is highlighted. This review provides theoretical and technical guidance for developing sustainable lignocellulose valorization processes based on rumen microorganisms.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 3","pages":"100107"},"PeriodicalIF":7.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustainable chemical technology: Core concepts, key subfields, and assessment approaches.","authors":"Máté Hartyányi, Roland Nagy","doi":"10.1016/j.bidere.2026.100105","DOIUrl":"10.1016/j.bidere.2026.100105","url":null,"abstract":"<p><p>Sustainable Chemical Technology provides an integrative framework for designing and deploying chemical products and manufacturing routes that reduce life-cycle environmental burdens while maintaining technical performance and economic viability. While green chemistry principles guide safer and more efficient transformations at the molecular level, sustainability outcomes at scale are often dominated by process and system factors, including separations and solvent management, utilities and energy integration, operability, and supply-chain constraints. This Short Communication proposes a concise working definition and a four-level interpretation structure spanning material, process, system, and life-cycle perspectives to support consistent boundary setting and comparison across technologies. Building on this framing, we summarize a compact taxonomy of core subfields feedstock and resources, reaction and process design, solvents and separations, and circularity and waste and outline typical intervention levers and trade-offs within each. Finally, we recommend a minimal assessment bundle that combines fast screening metrics with life-cycle thinking to reduce burden shifting and enable transparent decision-making from early research to industrial adoption.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 3","pages":"100105"},"PeriodicalIF":7.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution melting analysis for rapid and cost-effective detection of unnatural base pairs.","authors":"Sophie E J van der Vlugt, Jelke J Fros, Vitor A P Martins Dos Santos, Bauke Albada, Enrique Asin-Garcia","doi":"10.1016/j.bidere.2026.100090","DOIUrl":"10.1016/j.bidere.2026.100090","url":null,"abstract":"<p><p>Expansion of the genetic alphabet with unnatural base pairs (UBPs) enables new approaches in protein engineering, synthetic biology, and biocontainment. Such applications rely on faithful incorporation and retention of UBPs in semi-synthetic systems, making their detection and monitoring essential tools for xenobiology. Current methods for detecting UBPs in DNA frequently rely on labelling strategies, specialised reagents, or advanced analytical instrumentation. These approaches increase cost, technical complexity, and turnaround time, limiting accessibility and scalability of xenobiological experiments. Here, we establish high-resolution melting (HRM) analysis as a rapid and accessible method for detecting the UBP NaM-TPT3 based on differences in melting temperature of short amplicons. The approach can be directly appended to standard PCR workflows using commonly available qPCR instrumentation, enabling fast and cost-effective screening of UBP incorporation and stability in DNA. After optimisation of HRM-specific PCR conditions for efficient UBP incorporation, we demonstrate that HRM analysis produces clear and reproducible melting signatures that distinguish natural and unnatural sequences and detect defined variant mixtures. The method is validated using non-amplified DNA controls and LC-MS analysis. By enabling low-cost, workflow-integrated verification of UBP presence using standard laboratory infrastructures, HRM provides a practical screening tool that lowers barriers to experimentation and accelerated iterative development of expanded genetic systems.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100090"},"PeriodicalIF":7.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13223922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecology-microbiome engineering in Sauce-flavor Baijiu via Single-Cell Raman Spectroscopy.","authors":"Xi Sun, Xinyun Yi, Jia Zhang","doi":"10.1016/j.bidere.2026.100089","DOIUrl":"10.1016/j.bidere.2026.100089","url":null,"abstract":"<p><p>Sauce-flavor Baijiu owes its layered aroma to a diverse microbial consortium fermenting under extreme, open, solid-state conditions. High-throughput sequencing has revealed marked spatiotemporal heterogeneity in community composition, yet a fundamental composition-function disconnect persists: bulk omics average signals across heterogeneous micro-niches and cultivation recovers only a minor fraction of total diversity, leaving \"who is doing what\" unresolved. Closing this disconnect is a prerequisite for rational design of fermentation microbiomes and demands cell-resolved functional tools within an iterative engineering framework. This review proposes that Single-Cell Raman Spectroscopy (SCRS) and its derivatives, including D₂O-Raman activity mapping, scRACS-Seq phenotype-to-genome linkage, scRACS-Culture recovery of rare functional strains, and Intra-Ramanome Correlation Analysis (IRCA) predictive metabolic phenotyping, collectively provide a label-free, culture-independent toolkit suited to this role in solid-state matrices. We delineate how these single-cell insights feed each stage of a Design-Build-Test-Learn (DBTL) cycle, from phenotype-informed strain selection through consortium assembly and functional validation to data-driven iterative optimization. This convergence of cell-resolved functional dissection, synthetic ecology, and process analytical technologies establishes the foundation for advancing Sauce-flavor Baijiu from experience-dependent craftsmanship toward intelligent brewing.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100089"},"PeriodicalIF":7.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13206743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RecN: A tunable switch for DNA repair choice and stress tolerance in <i>Zymomonas mobilis</i>.","authors":"Saifu Pan, Xiaojie Wang, Jingjing He, Nan Peng","doi":"10.1016/j.bidere.2026.100088","DOIUrl":"10.1016/j.bidere.2026.100088","url":null,"abstract":"<p><p>Engineering polyploid industrial microorganisms is hindered by their intrinsic capacity to repair induced mutations, limiting the efficiency of genome editing and directed evolution. Using the ethanologenic bacterium <i>Zymomonas mobilis</i>- a polyploid alphaproteobacterium that exhibits exceptionally efficient microhomology-mediated end joining (MMEJ)- we demonstrate that RecN is essential for MMEJ and homologous recombination (HR) <i>in vivo</i>. Strikingly, a specialized mutant RecN-K35A, with strongly impaired ATP hydrolysis, specifically blocks MMEJ while leaving HR fully intact. The physiological importance of RecN-mediated MMEJ is highlighted by the cell elongation phenotype and increased stress sensitivity observed in the RecN-K35A mutant. Based on this connection, we developed a high-phosphorus cultivation strategy that increases cellular DNA content and significantly enhanced ethanol fermentation efficiency under industrial stress conditions. In summary, this work defines RecN as a key ATP-dependent effector of MMEJ and positions it as a potential engineering target for modulating DNA repair pathway choice and stress tolerance in <i>Z. mobilis</i>. Moreover, the essential role of RecN in both HR and MMEJ suggests that RecN-deficient polyploid strains could facilitate directed evolution by preventing repair of newly introduced mutations, offering a new strategy for strain improvement.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100088"},"PeriodicalIF":7.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial-type terpene synthases enable enhanced insect and fungal resistance in engineered plants.","authors":"Saif Ul Malook, Xinlu Chen, Bode A Olukolu, Alessandro Occhialini, Scott C Lenaghan, C Neal Stewart, Feng Chen","doi":"10.1016/j.bidere.2026.100087","DOIUrl":"10.1016/j.bidere.2026.100087","url":null,"abstract":"<p><p>A major challenge in crop improvement is enhancing resistance to diverse biotic stresses. Because terpenoids play key roles in chemical defense, an envisioned strategy is to introduce new terpene metabolic pathways into crops through engineering. Microbial-type terpene synthase-like (<i>MTPSL</i>) genes are widespread in nonseed plants but absent in seed plants. Here, we engineered terpene metabolism in <i>Nicotiana benthamiana</i> using <i>MTPSL</i> genes, enabling production of sesquiterpenes absent in flowering plants and enhanced resistance to pest insects and fungal pathogens. Two liverwort <i>MTPSL</i> genes, <i>RlMTPSL3</i> and <i>RlMTPSL4</i>, which produce sesquiterpenes absent from flowering plants, were selected for metabolic engineering. In <i>N. benthamiana</i>, both genes generated sesquiterpenes consistent with their <i>in vitro</i> activities, and co-expression yielded combined profiles. Co-expression of <i>RlMTPSL3</i> and <i>RlMTPSL4</i>, individually or together, with 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in sesquiterpene pathway, substantially increased sesquiterpene production. Bioassays of engineered tissues with two defoliating herbivores beet armyworm (<i>Spodoptera exigua</i>) and Colorado potato beetle (<i>Leptinotarsa decemlineata</i>) showed growth suppression and up to 30% mortality. The gut microbiome of beet armyworm feeding on engineered tissues showed differences from those feeding on control tissues, suggesting a potential mechanism underlying reduced pest insect performance. Engineered sesquiterpenes were recovered from larval frass, indicating stability through digestion. Transformed leaves emitted elevated sesquiterpenes as volatiles that repelled beet armyworm. In addition, extracts of engineered tissues inhibited the growth of <i>Fusarium oxysporum</i>, a fungal pathogen, by ∼50%. Together, these results demonstrate that <i>MTPSL</i>-based engineering can introduce new sesquiterpenes into flowering plants, providing a promising strategy for broad-spectrum crop protection.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100087"},"PeriodicalIF":7.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward development of soil-derived <i>Bacillus</i> isolates as lung cancer cytotoxic agents.","authors":"Dhruba Deb, Filippo Liguori, Bentley M Shuster, Ruoqi Huang, Stefani Shoreibah, Steven Wang, Nathan Emmanuel Rojas Ocampo, Kyle P Murray, Tal Danino","doi":"10.1016/j.bidere.2026.100074","DOIUrl":"10.1016/j.bidere.2026.100074","url":null,"abstract":"<p><p>The wide-ranging impact of the human microbiome on health and disease has sparked growing interest in employing bacteria as live therapeutics. Natural properties of bacteria have been enhanced using synthetic biology to treat diverse diseases, from infections to inflammation and cancer. However, a major obstacle in this area is identifying specific bacterial hosts and molecular payloads that are both safe and effective for specific diseases or cancers. In this study, we explored environmental microbial diversity as a promising source of new therapeutic agents that could be engineered for bacterial drug delivery systems. We collected and characterized soil bacteria from 25 urban public parks, then evaluated their secreted metabolites for anti-cancer activity using both monolayer and three-dimensional spheroid models of lung cancer. Metagenomic analysis, toxicity profiling, and co-culture assays revealed that several <i>Bacillus species</i> isolated from Manhattan park soils produced compounds with strong, dose-dependent cytotoxic effects on lung cancer cells. Furthermore, we demonstrated that <i>Bacillus subtilis</i>-a well-characterized, gram-positive model organism-was capable of colonizing lung tumor spheroids, suggesting its potential as a safe and effective chassis for bacterial cancer therapy. Complementing these experiments, we developed a mechanistic ordinary differential equation (ODE) model of the bacteria-spheroid co-culture that is consistent with our bacterial and spheroid growth data. Overall, our findings highlight a discovery platform for the screening of environmental microbes as chassis or payload sources for microbial cancer therapies.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100074"},"PeriodicalIF":7.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced growth of 1-butanol producing <i>Escherichia coli</i> via a metabolic buffer.","authors":"Haidong Yu, Haofeng Chen, Guojun Yang, Zhen Huang, Jieming Zhou, Dongjiang Lin, Junru Zhao, Yang Zhang, Jifeng Yuan","doi":"10.1016/j.bidere.2026.100086","DOIUrl":"10.1016/j.bidere.2026.100086","url":null,"abstract":"<p><p>1-Butanol is a C4 aliphatic alcohol that is widely used as a gasoline blendstock. In this study, we report an underexplored metabolic route for the <i>de novo</i> biosynthesis of 1-butanol in <i>Escherichia coli</i>. Specifically, the 1-butanol biosynthetic pathway comprises a redesigned <i>Clostridium</i>-derived pathway for butyryl-CoA synthesis, followed by a CoA-acylating aldehyde dehydrogenase (PduP from <i>Salmonella enterica</i>) and an endogenous alcohol dehydrogenase (YqhD from <i>E. coli</i>). We found that abolishing thioesterases to block the formation of butyrate byproduct would lead to deleterious effects on the cell growth. Upon introducing a metabolic buffering pathway towards polyhydroxyalkanoate biosynthesis, the toxicity caused by metabolic imbalance was alleviated, accompanied by enhanced cell growth and 1-butanol productivity. A similar strategy was also validated to be effective for improving the production of hexane-2,3-diol, a potential cosmetic component with high value. In summary, this work successfully demonstrates that the metabolic buffering strategy exerts a synergistic effect on enhancing biochemical production with improved carbon recovery efficiency.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"8 2","pages":"100086"},"PeriodicalIF":7.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}