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阿特罗威霉素的发现与生物合成,一种具有邻位二羟基肉桂酰链的抗结核和抗真菌环二肽。

Discovery and Biosynthesis of Atrovimycin, an Antitubercular and Antifungal Cyclodepsipeptide Featuring Vicinal-dihydroxylated Cinnamic Acyl Chain.

机构信息

State Key Laboratory of Biocontrol and Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences , Sun Yat-Sen University , Guangzhou 510275 , China.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology , South China Sea Institute of Oceanology, Chinese Academy of Sciences , Guangzhou 510301 , China.

出版信息

Org Lett. 2019 Apr 19;21(8):2634-2638. doi: 10.1021/acs.orglett.9b00618. Epub 2019 Apr 8.

DOI:10.1021/acs.orglett.9b00618
PMID:30958008
Abstract

Atrovimycin (1), a cyclodepsipeptide containing a unique vicinal-hydroxylated cinnamic acyl chain, was isolated and elucidated from Streptomyces atrovirens LQ13. The biosynthetic pathway of 1 was achieved, revealing cytochrome P450 (Avm43) and epoxide hydrolase (Avm29) enzymes constructing the vicinal-dihydroxy substitution, as well as a tailoring P450 (Avm28) enzyme catalyzing β-hydroxylation of the l-Phe moiety. Atrovimycin shows in vitro antifungal activity and antitubercular activity against Mycobacterium tuberculosis H37Rv both in vitro (with MIC of 2.5 μg/mL) and in vivo.

摘要

阿特罗霉素(1)是一种含有独特邻位羟化肉桂酰链的环二肽,从链霉菌属阿特罗沃里恩斯 LQ13 中分离并阐明。完成了 1 的生物合成途径,揭示细胞色素 P450(Avm43)和环氧化物水解酶(Avm29)酶构建邻位二羟基取代,以及修饰 P450(Avm28)酶催化 l-苯丙氨酸部分的β-羟化。阿特罗霉素在体外显示出抗真菌活性和抗结核活性,对结核分枝杆菌 H37Rv 均具有体外(MIC 为 2.5μg/mL)和体内活性。

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