Discovery and Engineered Overproduction of Antimicrobial Nucleoside Antibiotic A201A from the Deep-Sea Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652
Zhu, QH; Li, J; Ma, JY; Luo, MH; Wang, B; Huang, HB; Tian, XP; Li, WJ; Zhang, S; Zhang, CS; Ju, JH; jju@scsio.ac.cn
2012
发表期刊ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN0066-4804
卷号56期号:1页码:110-114
摘要Marinactinospora thermotolerans SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of mtdF, an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated mtdA furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator. To determine the role of MtdA in regulating A201A production, the mtdA gene was inactivated in frame and the resulting Delta mtdA mutant was fermented alongside the wild-type strain as a control. High-performance liquid chromatography (HPLC) analyses of fermentation extracts revealed that the Delta mtdA mutant produced A201A in a yield similar to 25-fold superior to that of the wild-type strain, thereby demonstrating that MtdA is a negative transcriptional regulator governing A201A biosynthesis. By virtue of its high production capacity, the Delta mtdA mutant constitutes an ideal host for the efficient large-scale production of A201A. These results validate M. thermotolerans as an emerging source of antibacterial agents and highlight the efficiency of metabolic engineering for antibiotic titer improvement.
部门归属[Zhu, Qinghua; Li, Jun; Ma, Junying; Luo, Minghe; Wang, Bo; Huang, Hongbo; Tian, Xinpeng; Zhang, Si; Zhang, Changsheng; Ju, Jianhua] Chinese Acad Sci, CAS Key Lab Marine Bioresources Sustainable Utili, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,S China Sea Inst Oceano, Guangzhou, Guangdong, Peoples R China; [Li, Jun] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China; [Li, Wenjun] Yunnan Univ, Yunnan Inst Microbiol, Kunming, Peoples R China
学科领域Microbiology ; Pharmacology & Pharmacy
语种英语
资助项目LMB
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/10030
专题中科院海洋生物资源可持续利用重点实验室
通讯作者jju@scsio.ac.cn
推荐引用方式
GB/T 7714
Zhu, QH,Li, J,Ma, JY,et al. Discovery and Engineered Overproduction of Antimicrobial Nucleoside Antibiotic A201A from the Deep-Sea Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2012,56(1):110-114.
APA Zhu, QH.,Li, J.,Ma, JY.,Luo, MH.,Wang, B.,...&jju@scsio.ac.cn.(2012).Discovery and Engineered Overproduction of Antimicrobial Nucleoside Antibiotic A201A from the Deep-Sea Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,56(1),110-114.
MLA Zhu, QH,et al."Discovery and Engineered Overproduction of Antimicrobial Nucleoside Antibiotic A201A from the Deep-Sea Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 56.1(2012):110-114.
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