ACS Synthetic Biology最新文献_第8页

Carbon Metabolism Modification in Bacillus subtilis for Improving Fengycin Production and Investigating Antifungal Activity of Its Homologous Components. 枯草芽孢杆菌碳代谢修饰提高风霉素产量及其同源成分抑菌活性研究

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18 Epub Date: 2025-06-17 DOI: 10.1021/acssynbio.5c00101

Dun-Ju Wang, Ming-Zhu Ding, Zheng-Jie Hou, Yong Zhang, Wei Shang, Tian-Xu Duan, Qiu-Man Xu, Jing-Sheng Cheng

{"title":"Carbon Metabolism Modification in Bacillus subtilis for Improving Fengycin Production and Investigating Antifungal Activity of Its Homologous Components.","authors":"Dun-Ju Wang, Ming-Zhu Ding, Zheng-Jie Hou, Yong Zhang, Wei Shang, Tian-Xu Duan, Qiu-Man Xu, Jing-Sheng Cheng","doi":"10.1021/acssynbio.5c00101","DOIUrl":"10.1021/acssynbio.5c00101","url":null,"abstract":"As a lipopeptide, fengycin exhibits environmentally friendly, safe, and long-lasting biocontrol efficacy. However, due to its complex structure and the challenges in chemical synthesis, it is primarily produced through biosynthesis. This study reports an improvement in fengycin production in Bacillus subtilis by engineering the central carbon metabolic pathway and blocking the carbon overflow pathway. The highest production achieved 1290.31 mg/L, representing a 2.05-fold increase compared to the original strain. Additionally, a coculture system was established in which Corynebacterium glutamicum supplied proline to strain CGF-PA, achieving a further increase in production to 2491.97 mg/L. The fengycin homologues were characterized using IMS-MS and separated by preparative liquid chromatography. The antifungal activities of fengycin homologues were quantitatively evaluated against Fusarium graminearum, Botrytis cinerea, Pyricularia oryzae, and Rhizoctonia solani, and their morphological changes were observed. The study also investigated the differences in antifungal activity among the fengycin variants. Components 4, 5, 6, and 7 exhibited relatively strong antifungal activity, and the various components of fengycin were found to work synergistically.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2644-2656"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315472","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}

引用次数: 0

Engineered Acinetobacter baylyi ADP1-ISx Cells Are Sensitive DNA Biosensors for Antibiotic Resistance Genes and a Fungal Pathogen of Bats. 工程贝氏不动杆菌ADP1-ISx细胞是敏感的DNA生物传感器的抗生素抗性基因和真菌病原体的蝙蝠。

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18 Epub Date: 2025-06-27 DOI: 10.1021/acssynbio.5c00360

Jeffrey Chuong, Keaton W Brown, Isaac Gifford, Dennis M Mishler, Jeffrey E Barrick

{"title":"Engineered Acinetobacter baylyi ADP1-ISx Cells Are Sensitive DNA Biosensors for Antibiotic Resistance Genes and a Fungal Pathogen of Bats.","authors":"Jeffrey Chuong, Keaton W Brown, Isaac Gifford, Dennis M Mishler, Jeffrey E Barrick","doi":"10.1021/acssynbio.5c00360","DOIUrl":"10.1021/acssynbio.5c00360","url":null,"abstract":"Naturally competent bacteria can be engineered into platforms for detecting environmental DNA. This capability could be used to monitor the spread of pathogens, invasive species, and resistance genes, among other applications. Here, we create Acinetobacter baylyi ADP1-ISx biosensors that detect specific target DNA sequences through natural transformation. We tested strains with DNA sensors that consisted of either a mutated antibiotic resistance gene (TEM-1 bla or nptII) or a counterselectable gene flanked by sequences from the fungus Pseudogymnoascus destructans, which causes white-nose syndrome in bats. Upon uptake of homologous DNA, recombination restored antibiotic resistance gene function or removed the counterselectable gene, enabling selection of cells that sensed the target DNA. The antibiotic resistance gene and P. destructans biosensors could detect as few as 3,000 or 5,000,000 molecules of their DNA targets, respectively, and their sensitivity was not affected by excess off-target DNA. These results demonstrate how A. baylyi can be reprogrammed into a modular platform for monitoring environmental DNA.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2488-2493"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511255","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}

引用次数: 0

Modular Design of a Copper Ion Biosensor Based on the MAPK Signaling Pathway in Saccharomyces cerevisiae. 基于酿酒酵母MAPK信号通路的铜离子生物传感器模块化设计

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18 Epub Date: 2025-06-25 DOI: 10.1021/acssynbio.5c00276

Tao Wang, Shuwen Ding, Jiao Xu, Guohao Cai, Yiqing Zhang, Yingxuan Qi, Yujia Jiang, Ping Zhang, Tianjing Wang, Fengxue Xin, Tao Shen, Guannan Liu

{"title":"Modular Design of a Copper Ion Biosensor Based on the MAPK Signaling Pathway in Saccharomyces cerevisiae.","authors":"Tao Wang, Shuwen Ding, Jiao Xu, Guohao Cai, Yiqing Zhang, Yingxuan Qi, Yujia Jiang, Ping Zhang, Tianjing Wang, Fengxue Xin, Tao Shen, Guannan Liu","doi":"10.1021/acssynbio.5c00276","DOIUrl":"10.1021/acssynbio.5c00276","url":null,"abstract":"Copper ion poses serious threats to both the environment and human health. To develop a yeast biosensor with reduced background noise and enhanced detection sensitivity, we constructed a quorum-sensing module with amplified positive feedback. This biosensor employs a copper ion-pheromone communication system, which allows haploid a-type yeast (MATa) to express the α-pheromone gene (mfα2) under the control of the copper ion-inducible promoter pCUP1. The α-pheromone activates the mitogen-activated protein kinase (MAPK) signaling pathway, which in turn induces the expression of the green fluorescent protein (GFP) gene via the pheromone-inducible promoter pprm1. To improve the performance of the biosensor, we optimized the prm1 promoter and constructed the Ste5ΔN-CTM chassis. Specifically, the promoter intensity was improved by converting the three nonconsensus Pheromone Response Elements (PRE) in pprm1 into consensus PRE sequences, resulting in the prm1 Pro promoter. The Ste5ΔN-CTM strain continuously activates the MAPK signaling pathway. Next, to offset the loss of sensitivity and dynamic response range caused by endogenous pheromone degradation, we knocked out the pheromone degradation gene bar1 using CRISPR-Cas9 gene editing technology. Additionally, we established a functional model relating the copper ion concentration to the GFP signal output. In conclusion, this study designed a modular copper ion biosensor system by integrating sensing, amplification, and signal-reporting components, laying a foundation for the development of biosensors for other heavy metals.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2854-2864"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493142","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}

引用次数: 0

Heterologous Production of Levopimaradiene in Saccharomyces cerevisiae. 酿酒酵母异源生产左旋旋己二烯的研究。

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18 Epub Date: 2025-07-10 DOI: 10.1021/acssynbio.5c00105

Xiaomeng Fu, Xiaoru Zuo, Kunqiang Hong, Chuanbo Zhang, Wenyu Lu

{"title":"Heterologous Production of Levopimaradiene in Saccharomyces cerevisiae.","authors":"Xiaomeng Fu, Xiaoru Zuo, Kunqiang Hong, Chuanbo Zhang, Wenyu Lu","doi":"10.1021/acssynbio.5c00105","DOIUrl":"10.1021/acssynbio.5c00105","url":null,"abstract":"Levopimaradiene (LP) is a precursor of the important anticancer compound ginkgolide. However, the current low synthetic yield in yeast limits the progress of the microbial ginkgolide synthesis pathway. In order to increase the synthetic flux of LP in S. cerevisiae, we first overexpressed the fusion protein of Bts1p-Erg20p(F96C) in a geranylgeranyl diphosphate (GGPP)-enhanced strain. The LP concentration was 20.36 mg L-1 when the T79LPSM593I/Y700F gene was integrated. The overexpression of a series of genes in the mevalonate (MVA) pathway led to a significant increase in the LP yield, reaching 59.37 mg L-1. Next, the spheroplast protein Y (SPY) tag was fused to the N-terminus of LP synthase, which increased the yield of LP to 82.21 mg L-1. In order to consume the accumulated precursor GGPP and balance the expression levels of BTS1 (encoding geranylgeranyl diphosphate synthase) and LPS (encoding levopimaradiene synthase) genes, the expression copy numbers of BTS1 and LPS genes were regulated using scaffold protein technology. Subsequently, an LP yield of 215.50 mg L-1 was achieved via fed-batch fermentation in a 5-L bioreactor, which represents the highest reported level in S. cerevisiae currently. This lays the foundation for advancing the heterologous synthesis of ginkgolides and provides a reference for the efficient synthesis of natural products in S. cerevisiae.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2657-2666"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598898","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}

引用次数: 0

Tet Transgene Activation is Disrupted in Lipogenic Triple Negative Breast Cancer Cells. 脂源性三阴性乳腺癌细胞中Tet转基因激活被破坏。

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18 Epub Date: 2025-07-08 DOI: 10.1021/acssynbio.4c00851

Ashley Townsel, Yifei Wu, Maya Jaffe, Cara Shields, Karmella A Haynes

{"title":"Tet Transgene Activation is Disrupted in Lipogenic Triple Negative Breast Cancer Cells.","authors":"Ashley Townsel, Yifei Wu, Maya Jaffe, Cara Shields, Karmella A Haynes","doi":"10.1021/acssynbio.4c00851","DOIUrl":"10.1021/acssynbio.4c00851","url":null,"abstract":"A critical challenge for mammalian cell engineering is the unexpected response of transgenes to native transcriptional regulation pathways. One transgene can show different levels of expression at different genomic sites, in different cell types, and under different growth conditions. Collisions between transcription and DNA replication, heterochromatin encroachment, and viral defense have been linked to transgene silencing. In this study, we identify fatty acid metabolism as another mediator of transgene behavior. Adipocyte secretome-induced lipogenesis in epithelial breast cancer cells was accompanied by the loss of expression from a Tet-TA regulated pCMV-AmCyan reporter transgene. Transcription profiling showed activation of lipid droplet biosynthesis, and repression of loci across the genome, consistent with the idea that lipogenesis affects the availability of substrates and cofactors for global chromatin remodeling. Preinduction of pCMV prevented full silencing during lipogenesis. Our results provide new insights into the influence of shifting metabolic states on transgene behavior.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":"2455-2464"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18

Satoshi Ishida, Arno Gundlach, Clayton W. Kosonocky and Andrew D. Ellington*,

引用次数: 0

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18

Ariel Chen, Shachar Gat , Lior Ohana, Evgenee Yekymov , Yoav Tsori and Anne Bernheim-Groswasser *,

引用次数: 0

IF 3.7 2区生物学

ACS Synthetic Biology Pub Date : 2025-07-18

Weijie Ou, Jing Dan, Xuzhen Guo*, Qiong Liu* and Lei Tan*,