Synthetic and Systems Biotechnology最新文献

{"title":"Corrigendum to “Morphology-engineered alleviation of mycelial aggregation in Streptomyces chassis for potentiated production of secondary metabolites” [Synth Syst Biotechnol 10 (3) (2025) 1059–1069]","authors":"Shuo Liu , Fei Xiao , Lanxin Lv , Meiyan Wang , Wenli Li , Guoqing Niu","doi":"10.1016/j.synbio.2025.11.006","DOIUrl":"10.1016/j.synbio.2025.11.006","url":null,"abstract":"","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 183-184"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular landscape analysis of azinothricin-type natural products enables the identification of kettapeptin from Streptomyces durmitorensis","authors":"Huixue Chen ,&nbsp;Yan Gao ,&nbsp;Shixue Jin ,&nbsp;Qian Yun ,&nbsp;Xinchen Ruan ,&nbsp;Xudong Qu ,&nbsp;Chun Lei","doi":"10.1016/j.synbio.2025.12.013","DOIUrl":"10.1016/j.synbio.2025.12.013","url":null,"abstract":"<div><div>The azinothricin family of hybrid hexadepsipeptide-polyketide natural products exhibit remarkable bioactivities, including potent antibacterial, antitumor, antimalarial and anti-inflammatory activities. However, only a few azinothricin-type natural products are currently known, and the biosynthetic potential of microbes remains underexplored. In this work, 137 candidate biosynthetic gene clusters (BGCs) were identified using a genome-mining strategy based on cblaster homology screening. Furthermore, <em>Streptomyces durmitorensis</em> DSM 41863 was prioritized for in-depth experiment due to its unique PKS module expansion, leading to the discovery of kettapeptin, the azinothricin-type metabolite isolated from this species for the first time. Additionally, a putative biosynthetic pathway for kettapeptin was proposed. This work expands the azinothricin-type BGC landscape and establishes <em>S</em>. <em>durmitorensis</em> DSM 41863 as a genetically tractable platform for bioengineering novel derivatives.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 265-273"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions and optimization of soft law in the international governance of synthetic biology: The predicament of hard law vs. the rise of soft law","authors":"Yu Qin ,&nbsp;Jiaxiang Hu ,&nbsp;Kezhen Su","doi":"10.1016/j.synbio.2025.11.005","DOIUrl":"10.1016/j.synbio.2025.11.005","url":null,"abstract":"<div><div>Synthetic biology, as an emerging field that integrates life sciences and engineering technology, is driving profound transformations in global science, ethics, and legal systems. In international legal framework, the Biological Weapons Convention (BWC) and the Convention on Biological Diversity (CBD) have established initial hard law governance systems. However, these frameworks still face structural limitations in terms of technical adaptability, the scope of provisions, and institutional coordination. Soft law, with its flexibility, non-binding nature, and ability to build consensus, is increasingly becoming an essential supplement to the international response to the ethical risks of synthetic biology. International organizations, industry alliances, and non-governmental actors are constructing a multi-layered soft law governance network through ethical guidelines, policy recommendations, and codes of conduct, providing institutional support for risk identification, technology classification, and behavioral guidance. Soft law is well-suited to perform the roles of guiding and providing feedback in governance, while hard law should focus on the construction of systems of rights and responsibilities and the establishment of obligations. There is a collaborative governance model that integrates both soft and hard law. This model, characterized by “soft law guidance, hard law consolidation, and soft law feedback,” aims to create a flexible and enforceable governance framework. This approach ensures that soft law provides a timely and adaptive starting point, hard law offers a uniform and accountable foundation, and a feedback loop allows for continuous adjustment based on practical experience.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 134-151"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RECC: A Red/ET–CRISPR/Cas9-based system enabling genome mining of marine Pseudoalteromonas for novel natural products","authors":"Zong-jie Wang ,&nbsp;Haibo Zhou ,&nbsp;Youming Zhang ,&nbsp;Fu Yan ,&nbsp;Liujie Huo ,&nbsp;Xiaotong Wang","doi":"10.1016/j.synbio.2025.12.015","DOIUrl":"10.1016/j.synbio.2025.12.015","url":null,"abstract":"<div><div>Marine microorganisms possess vast biosynthetic potential, yet most of their biosynthetic gene clusters (BGCs) remain transcriptionally silent under laboratory conditions. Genetic intractability has been a major barrier to activating these cryptic pathways. Here, we present RECC, an integrated <u>R</u>ed/<u>E</u>T–<u>C</u>RISPR/<u>C</u>as9 system that enables seamless, marker-free genome editing in marine bacteria. RECC couples Red/ET recombineering with CRISPR/Cas9-mediated cleavage, allowing the incorporation of homology arms and protospacers into a single construct through one-step Gibson assembly, thereby substantially simplifying the engineering process. Using <em>Pseudoalteromonas flavipulchra</em> DSM 14401 as a model, we employed RECC to replace the native promoter of a silent nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) hybrid gene cluster with a strong constitutive promoter. This targeted activation led to the production of a series of previously unknown cyclolipopeptides, designated flavipulchrins. Structural characterization and bioinformatic analysis revealed a plausible biosynthetic pathway for these metabolites. Collectively, RECC provides a robust and generalizable genome-editing platform that facilitates the systematic exploration of biosynthetic potential in genetically recalcitrant marine microorganisms.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 342-351"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo synthesis of L-2-aminobutyric acid in Escherichia coli based on multi-layered metabolic engineering strategies","authors":"Zhenqiang Zhao ,&nbsp;Yizheng Liu ,&nbsp;Rongshuai Zhu ,&nbsp;Fengyu Yang ,&nbsp;Zhifei Liu ,&nbsp;Jiajia You ,&nbsp;Xuewei Pan ,&nbsp;Jianming Yang ,&nbsp;Zhiming Rao","doi":"10.1016/j.synbio.2026.01.004","DOIUrl":"10.1016/j.synbio.2026.01.004","url":null,"abstract":"<div><div>L-2-Aminobutyric acid (L-2-ABA) is a non-proteinogenic amino acid and an important chiral intermediate widely used in pharmaceuticals and fine chemicals. However, its fermentative production is limited by intermediate toxicity and imbalanced metabolic flux. In this study, <em>Escherichia coli</em> was systematically engineered for efficient <em>de novo</em> synthesis of L-2-ABA using a multi-layer metabolic engineering strategy. A quorum-sensing–based dynamic control circuit was introduced to decouple cell growth from 2-oxobutyric acid formation, thereby alleviating precursor toxicity and improving flux coordination. Combined with optimization of the L-2-ABA conversion pathway, model-guided carbon flux redistribution, cofactor regeneration, and tuning of global transcriptional regulation, a high-performance production strain was obtained without the need for antibiotics or inducers. The final engineered strain ABA40 achieved 45.3 g/L L-2-ABA with a yield of 0.31 g/g glucose in a 72 h fed-batch fermentation. This study demonstrates the effectiveness of dynamic and integrated metabolic engineering strategies for the biosynthesis of non-natural amino acids.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 374-382"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A growth-coupled progesterone-responsive biosensor for high-throughput microfluidic screening in Saccharomyces cerevisiae","authors":"Yucheng Hu ,&nbsp;Jinde Chen ,&nbsp;Shaofang Tian ,&nbsp;Yang Zhang ,&nbsp;Zhiqian Zhang ,&nbsp;Ao Jiang ,&nbsp;Yi-Rui Wu ,&nbsp;Baoshun Zhang","doi":"10.1016/j.synbio.2025.12.004","DOIUrl":"10.1016/j.synbio.2025.12.004","url":null,"abstract":"<div><div>Poor aqueous solubility of steroid precursors, such as pregnenolone and progesterone, limits microbial biotransformation and high-throughput strain screening, representing a bottleneck for strain improvement and potential industrial applications.</div><div>To address this, we developed a growth-coupled progesterone-responsive biosensor in <em>Saccharomyces cerevisiae</em>, integrated with a hydroxypropyl-β-cyclodextrin (HP-β-CD) system to enhance intracellular steroid availability. The biosensor links progesterone formation to cell growth and fluorescence, with selection stringency finely tuned via an IPTG-inducible lac operator and 3-aminotriazole (3-AT) to suppress low-producing cells. Coupled with atmospheric and room temperature plasma (ARTP) mutagenesis, the growth-coupled biosensor–FADS platform identified five yeast variants capable of improved conversion of pregnenolone to progesterone while expressing 3β-hydroxysteroid dehydrogenase (3β-HSD) without altering the enzyme itself. The progesterone production of these selected variants was subsequently validated using 1 mM pregnenolone as the substrate, showing 2.0–3.37-fold higher titers than the wild-type strain, demonstrating proof-of-concept. Microfluidic droplet encapsulation allowed clear separation of high-producers, highlighting the platform's selectivity, robustness, and scalability. This synthetic biology–driven system integration platform provides a practical, modular, and high-throughput strategy for screening poorly water-soluble steroid-producing yeast. It is adaptable to other bioactive molecules, can support future enzyme evolution, and demonstrates potential for broader biotechnological applications.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 301-311"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A synergistic strategy of metabolic engineering and flocculation recycling for enhanced acetoin production in Zymomonas mobilis","authors":"Weiwei Bao ,&nbsp;Qiqun Peng ,&nbsp;Hongxiang Yu ,&nbsp;Hongwei Yang ,&nbsp;Shihui Yang","doi":"10.1016/j.synbio.2025.12.014","DOIUrl":"10.1016/j.synbio.2025.12.014","url":null,"abstract":"<div><div>Acetoin, a valuable platform chemical, faces sustainability challenges in its traditional energy-intensive synthesis. Microbial fermentation using microorganisms such as <em>Zymomonas mobilis</em> offers a promising alternative. To overcome metabolic limitations and process inefficiencies of economic acetoin production, we integrated strategies of metabolic engineering, transcriptomic-guided analysis, flocculation-based cell recycling, and non-food feedstock utilization. A dominant metabolism compromised intermediate (DMCI) chassis of <em>Z. mobilis</em> was constructed by deleting ethanol production and acetoin degradation pathways. Transcriptomics was then employed to identify and knockout latent competing pathway genes of <em>ZMO0318</em> and <em>ZMO1576</em> to enhance acetoin production. The engineered strain also tolerated to inhibitors in lignocellulosic hydrolysates, and fed-batch fermentation achieved an acetoin titer of 73 g/L. Furthermore, self-flocculating phenotype was engineered via <em>ZMO1082</em> modification to enable efficient cell recycling over multiple batches for production cost reduction. This study thus establishes a synergistic strategy to enhance acetoin production, highlighting the role of combining metabolic engineering, omics analyses, and processing engineering for economic biochemical production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 401-410"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering ω-transaminase for efficient dihydroxyacetone transamination in serinol biosynthesis starting from methanol","authors":"Ya Wu ,&nbsp;Chonghao Guo ,&nbsp;Lizhen Deng ,&nbsp;Derui Zhang ,&nbsp;Yutong Bie ,&nbsp;Yuxin He ,&nbsp;Gen Lu ,&nbsp;Shewei Hu ,&nbsp;Ruiqi Zeng ,&nbsp;Zeyang Li ,&nbsp;Xudong Xu ,&nbsp;Longjiang Yu","doi":"10.1016/j.synbio.2025.11.004","DOIUrl":"10.1016/j.synbio.2025.11.004","url":null,"abstract":"<div><div>Serinol (2-amino-1,3-propanediol) is an important pharmaceutical intermediate, but conventional chemical or microbial routes are hampered by high energy demand, product toxicity, or complex regulation. Here, we report a modular cell-free enzyme cascade, termed the methanol-to-serinol pathway (MSP), that efficiently converts methanol—a low-cost C1 feedstock—into serinol with high carbon yield. The cascade comprises two modules: Module 1 employs an alcohol oxidase and an engineered formolase to generate dihydroxyacetone (DHA), while Module 2 uses a tailored ω-transaminase for direct one-step amination. To overcome the rate-limiting DHA amination, we applied an “ALF” scanning strategy and identified a triple-mutant Cv-ωTA (Y153F/Y168F/C418F) with 6.3-fold higher specific activity than the wild type. Fitness landscape analysis revealed strong non-additive interactions, highlighting the synergistic effect of these three mutations. Molecular dynamics simulations revealed structural changes underlying the activity boost. By incorporating a pyruvate-removal system to drive the equilibrium toward product formation, the integrated cascade achieved 43.86 mM (4 g/L) serinol from 150 mM methanol in 7 h, corresponding to 87.7 % carbon yield and a productivity of 0.57 g/L/h. This work establishes a carbon-efficient route for serinol biosynthesis and provides a generalizable strategy for sustainable C1 biomanufacturing.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 71-81"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial engineering of enzyme and pathway for efficient β-farnesene bioproduction in Yarrowia lipolytica","authors":"Hongyang Chen ,&nbsp;Liqiu Su ,&nbsp;Zhen Yao ,&nbsp;Kaizhi Jia ,&nbsp;Zongjie Dai ,&nbsp;Qinhong Wang","doi":"10.1016/j.synbio.2025.10.016","DOIUrl":"10.1016/j.synbio.2025.10.016","url":null,"abstract":"<div><div>β-farnesene, a natural sesquiterpene compound, has gained significant attention due to its versatile applications in agriculture, industry, biofuels, and related fields. Microbial biosynthesis offers an environmentally sustainable approach for its commercial-scale production. In order to enhance its production efficiency, further exploration of key rate-limiting steps is required. Here, through directed evolution of the essential β-farnesene synthase, we obtained an optimal variant (AaFS^{T196A/M356T/E380G}), demonstrating 2.29-fold enhancement in β-farnesene titer relative to wild-type. Structural elucidation revealed that the distal mutations mediate allosteric modulation of the catalytic core significantly improving the conversion efficiency of farnesyl diphosphate (FPP) to β-farnesene. Then comprehensive pathway engineering, including the mevalonate pathway amplification, acetyl-CoA precursor enhancement, competitive pathway elimination, and auxotrophic restoration, were carried out in <em>Yarrowia lipolytica</em>, resulting in a high-performance strain FS18 capable of producing 3.41 g/L β-farnesene in shake-flask cultures. Notably, scale up fermentation in 5 L bioreactors yielded a titer of 45.69 g/L, the highest concentration reported in <em>Y</em>. <em>lipolytica</em> to date. This study provided mechanistic insights into terpene synthase engineering and a practical framework for high-level terpenoid biosynthesis in <em>Y. lipolytica</em>.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 32-41"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered dual-fluorescence functional nucleic acid-based CRISPR/Cas12a biosensor for label-free ratiometric detection of site-specific DNA methylation","authors":"Wen Tian ,&nbsp;Songcheng Yu ,&nbsp;Kaiyang Zhang ,&nbsp;Tao Liu ,&nbsp;Lihua Ding ,&nbsp;Peng Zhang","doi":"10.1016/j.synbio.2025.11.003","DOIUrl":"10.1016/j.synbio.2025.11.003","url":null,"abstract":"<div><div>The CRISPR/Cas12a system holds significant promise for biomedical applications. Nevertheless, the commonly used reporter, fluorophore–quencher-labeled substrates, is hindered by labor-intensive synthesis procedures and high costs, while also relying on a single-photon method and being vulnerable to environmental interference. Herein, a label-free dual-fluorescent functional nucleic acid (DFFNA) was engineered, comprising an aptamer domain for auramine O (AO) recognition and a dSpacer-integrated DNA duplex region for 5,6,7-trimethyl-1,8-naphthyridin-2-amine (ATMND) binding. The fluorescence of AO and ATMND can be enhanced and quenched, respectively, when bound to DFFNAs. The fluorescence intensity ratio between ATMND and AO increased significantly following the cleavage of DFFNAs by activated Cas12a, thus offering a universal, label-free, ratiometric fluorescent reporter for the CRISPR/Cas12a system. To explore the application of the DFFNA-based CRISPR/Cas12a system, a novel biosensor was developed to detect site-specific DNA methylation. It employs a methylation-sensitive restriction enzyme to recognize methylation sites, Cas12a for site-specific DNA identification and signal amplification, and DFFNAs to produce ratiometric fluorescence. The assay demonstrated remarkable specificity and sensitivity, with a limit of detection of 152 pM, due to the high resolution and <em>trans</em>-cleavage activity of Cas12a. The rationally designed and label-free DFFNAs enhance stability, increase flexibility, and reduce cost. The observable color change and smartphone imaging capability facilitate portable, point-of-care testing. Specifically, the biosensor demonstrated excellent specificity by differentiating colorectal cancer patients from healthy individuals. Consequently, this work presents a superior label-free and ratiometric fluorescent reporter for the CRISPR/Cas12a system, which offers a promising strategy for DNA methylation detection in clinical settings.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"12 ","pages":"Pages 52-58"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}