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The roles of genes associated with regulation, transportation, and macrocyclization in desotamide biosynthesis in Streptomyces scopuliridis SCSIO ZJ46
Ding, Wenjuan1; Dong, Yuliang; Ju, Jianhua1; Li, Qinglian
2020
Source PublicationAPPLIED MICROBIOLOGY AND BIOTECHNOLOGY
ISSN0175-7598
Volume104Issue:6Pages:2603
AbstractThe deep-sea-derived microbe Streptomyces scopuliridis SCSIO ZJ46 produces desotamides A-D. Notably, desotamides A and B display antibacterial activities against pathogenic Gram-positive Streptococcus pneumoniae NCTC 7466, Staphylococcus aureus ATCC 29213, and the methicillin-resistant clinical isolate Staphylococcus epidermidis (MRSE) shhs-E1. The 39-kb desotamide biosynthetic gene cluster (dsa) has previously been identified and heterologously expressed in S. coelicolor M1152 for the purposes of assigning dsa gene functions. In this work, we identified seven genes in the dsa cluster including three regulatory genes (dsaA, dsaM, and dsaN), two transporter genes (dsaK and dsaL), and two other genes, dsaB (annotated as a phosphate synthase) and dsaJ (a PBP-type thioesterase). The DsaA and DsaN were unambiguously shown to be positive regulators of desotamide biosynthesis, and consistent with these roles, inactivation of either gene completely abolished desotamide production. Moreover, overexpression of dsaA or dsaN (independent of each other) was shown to improve desotamide titers. Production of desotamides in M1152/07-6H::dsaA strain was 2.4-fold greater than that in the heterologous dsa expression strain M1152/07-6H whereas desotamide titers from the M1152/07-6H::dsaN strain were about twice that of M1152/07-6H. In addition, inactivation of dsaB and dsaJ (independent of each other) completely abolished desotamide production, indicating their indispensability for desotamide assembly. These studies provide new insights into the functions and combinatorial biosynthetic potentials of seven key genes within the dsa biosynthetic gene cluster. Findings reported here are likely to facilitate further efforts aimed at assessing and developing the desotamides and related analogs for future applications.
DepartmentLMB
KeywordDesotamide Biosynthesis Regulator ABC transporter IGPS PBP-type thioesterase
Funding OrganizationNatural Key Research and development Program of China [2017YFD0201400]; China NSFNational Natural Science Foundation of China (NSFC) [31670087, 31400072, U1706206]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; Guangdong NSFNational Natural Science Foundation of Guangdong Province [2016A030312014]; Pearl River S&T Nova Program of Guangzhou [201806010109]; Special Support Program for Training High-Level Talents in Guangdong [2016TQ03R288]; CASChinese Academy of Sciences [XDA13020302-2] ; Natural Key Research and development Program of China [2017YFD0201400]; China NSFNational Natural Science Foundation of China (NSFC) [31670087, 31400072, U1706206]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; Guangdong NSFNational Natural Science Foundation of Guangdong Province [2016A030312014]; Pearl River S&T Nova Program of Guangzhou [201806010109]; Special Support Program for Training High-Level Talents in Guangdong [2016TQ03R288]; CASChinese Academy of Sciences [XDA13020302-2]
DOI10.1007/s00253-020-10414-4
Funding OrganizationNatural Key Research and development Program of China [2017YFD0201400]; China NSFNational Natural Science Foundation of China (NSFC) [31670087, 31400072, U1706206]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; Guangdong NSFNational Natural Science Foundation of Guangdong Province [2016A030312014]; Pearl River S&T Nova Program of Guangzhou [201806010109]; Special Support Program for Training High-Level Talents in Guangdong [2016TQ03R288]; CASChinese Academy of Sciences [XDA13020302-2] ; Natural Key Research and development Program of China [2017YFD0201400]; China NSFNational Natural Science Foundation of China (NSFC) [31670087, 31400072, U1706206]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; Guangdong NSFNational Natural Science Foundation of Guangdong Province [2016A030312014]; Pearl River S&T Nova Program of Guangzhou [201806010109]; Special Support Program for Training High-Level Talents in Guangdong [2016TQ03R288]; CASChinese Academy of Sciences [XDA13020302-2]
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/18506
Collection中科院海洋生物资源可持续利用重点实验室
Affiliation1.Chinese Acad Sci, Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,South China Sea Inst Oc, 164 West Xingang Rd, Guangzhou 510301, Peoples R China
2.Univ Chinese Acad Sci, Coll Oceanol, 19 Yuquan Rd, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Ding, Wenjuan,Dong, Yuliang,Ju, Jianhua,et al. The roles of genes associated with regulation, transportation, and macrocyclization in desotamide biosynthesis in Streptomyces scopuliridis SCSIO ZJ46[J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,2020,104(6):2603, 2610.
APA Ding, Wenjuan,Dong, Yuliang,Ju, Jianhua,&Li, Qinglian.(2020).The roles of genes associated with regulation, transportation, and macrocyclization in desotamide biosynthesis in Streptomyces scopuliridis SCSIO ZJ46.APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,104(6),2603.
MLA Ding, Wenjuan,et al."The roles of genes associated with regulation, transportation, and macrocyclization in desotamide biosynthesis in Streptomyces scopuliridis SCSIO ZJ46".APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 104.6(2020):2603.
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