Rescrutiny of the sansanmycin biosynthetic gene cluster leads to the discovery of a novel sansanmycin analogue with more potency against Mycobacterium tuberculosis.,The Journal of Antibiotics

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Rescrutiny of the sansanmycin biosynthetic gene cluster leads to the discovery of a novel sansanmycin analogue with more potency against Mycobacterium tuberculosis.
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2019-07-24 , DOI: 10.1038/s41429-019-0210-z
Yuanyuan Shi _{1,

2} , Xinwei Wang ₂ , Ning He ₂ , Yunying Xie ₂ , Bin Hong _{1,

2}

Affiliation

A novel sansanmycin analogue, sansanmycin Q (1), was identified by genome mining from the fermentation broth of Streptomyces sp. SS (CPCC 200442). In comparison with other sansanmycin compounds, sansanmycin Q has an extra glycine residue at the N-terminus of the pseudopeptide backbone. The additional glycine was proved to be assembled to sansanmycin A by SsaB, a tRNA-dependent aminoacyltransferase, based on the results of rescrutiny of sansanmycin biosynthetic gene cluster, and then overexpression and knockout of ssaB in the wild-type strain. The structure of sansanmycin Q was assigned by interpretation of NMR and mass spectral data. The results of the bioassay disclosed that sansanmycin Q exhibited more potency against Mycobacterium tuberculosis H37Rv and a rifampicin- and isoniazid-resistant strain than sansanmycin A.

中文翻译：

对sansanmycin生物合成基因簇的详细研究导致发现了一种新型的sansanmycin类似物，其对结核分枝杆菌的效力更高。

从链霉菌属（Streptomyces sp。）的发酵液中进行基因组挖掘，鉴定了一种新型的sansanmycin类似物sansanmycin Q（1）。SS（CPCC 200442）。与其他sansanmycin化合物相比，sansanmycin Q在伪肽主链的N末端有一个额外的甘氨酸残基。根据对sansanmycin生物合成基因簇的审查结果，再通过野生型菌株中ssaB的过表达和敲除，证明了额外的甘氨酸已通过tsa依赖的tRNA氨基转移酶SsaB组装到sansanmycin A上。Sansanmycin Q的结构通过NMR和质谱数据解释来确定。生物测定的结果表明，桑山霉素Q对结核分枝杆菌H37Rv以及耐利福平和异烟肼的菌株表现出比桑山霉素A更强的效力。

更新日期：2019-11-18

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