Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Stefan-Meier-Strasse 19 VF, 79104, Freiburg im Breisgau, Germany.
Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario, K7L 3N6, Canada.
Chembiochem. 2018 Feb 2;19(3):272-279. doi: 10.1002/cbic.201700428. Epub 2017 Dec 18.
In this study, we report that Streptomyces asterosporus DSM 41452 is a producer of new molecules related to the nonribosomal cyclodepsipeptide WS9326A and the polyketide annimycin. S. asterosporus DSM 41452 is shown to produce six cyclodepsipeptides and peptides, WS9326A to G. Notably, the compounds WS9326F and WS9326G have not been described before. The genome of S. asterosporus DSM 41452 was sequenced, and a putative WS9326A gene cluster was identified. Gene-deletion experiments confirmed that this cluster was responsible for the biosynthesis of WS9326A to G. Additionally, a gene-deletion experiment demonstrated that sas16 encoding a cytochrome P450 monooxygenase was involved in the synthesis of the novel (E)-2,3-dehydrotyrosine residue found in WS9326A and its derivatives. An insertion mutation within the putative annimycin gene cluster led to the production of a new annimycin derivative, annimycin B, which exhibited modest inhibitory activity against Plasmodium falciparum.
在这项研究中，我们报告链霉菌属 asterosporus DSM 41452 是一种新型分子的生产者，这些新型分子与非核糖体环二肽 WS9326A 和聚酮类 annimycin 有关。链霉菌属 asterosporus DSM 41452 被证明可以产生六种环二肽和肽，包括 WS9326A 到 G。值得注意的是，化合物 WS9326F 和 WS9326G 以前没有被描述过。对链霉菌属 asterosporus DSM 41452 的基因组进行了测序，并鉴定出一个假定的 WS9326A 基因簇。基因缺失实验证实，这个基因簇负责 WS9326A 到 G 的生物合成。此外，基因缺失实验表明，编码细胞色素 P450 单加氧酶的 sas16 参与了 WS9326A 及其衍生物中新型（E）-2,3-脱水酪氨酸残基的合成。在假定的 annimycin 基因簇内的插入突变导致了 annimycin B 的产生，这是 annimycin 的一种新衍生物，对疟原虫表现出适度的抑制活性。
