Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides

被引:44
作者
Chen, Ruidong [1 ]
Zhang, Qingbo [1 ]
Tan, Bin [1 ]
Zheng, Liujuan [1 ]
Li, Huixian [1 ]
Zhu, Yiguang [1 ]
Zhang, Changsheng [1 ]
机构
[1] Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med,RNAM Ctr Marine, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China
关键词
PEPTIDYL NUCLEOSIDE ANTIBIOTICS; POLYKETIDE SYNTHASE; LOBOPHORIN BIOSYNTHESIS; PACIDAMYCIN GROUP; VANCOMYCIN GROUP; STREPTOMYCES SP; TETR FAMILY; IDENTIFICATION; REVEALS; (S)-3,5-DIHYDROXYPHENYLGLYCINE;
D O I
10.1021/acs.orglett.7b02878
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in. marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically Manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamide (TPMS)-A (1) and B (3), and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl Moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2.
引用
收藏
页码:5697 / 5700
页数:4
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