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Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics

文献类型： 外文期刊

作者： Li, Ling Yu 1 ; Hu, Yi Ling 1 ; Sun, Jia Lin 1 ; Yu, Long Bo 1 ; Shi, Jing 1 ; Wang, Zi Ru 1 ; Guo, Zhi Kai 2 ; Zhang, Bo 1 ; Guo, Wen Jie 1 ; Tan, Ren Xiang 1 ; Ge, Hui Ming 1 ;

作者机构： 1.Nanjing Univ, Chem & Biomed Innovat Ctr ChemBIC, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China

2.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Key Lab Biol & Genet Resources Trop Crops, Minist Agr, Haikou 571101, Hainan, Peoples R China

期刊名称：CHEMICAL SCIENCE （ 影响因子：9.969； 五年影响因子：9.974 ）

ISSN： 2041-6520

年卷期： 2022 年 13 卷 43 期

页码：

收录情况： SCI

摘要： Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1). Through genetic and biochemical studies, we elucidated the biosynthetic pathway of 1, which involves a complex glycosylation process. Our work discloses nature's huge capacity to generate diverse tetracyclines and expands the chemical diversity of tetracyclines.

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