Journal
CHEMBIOCHEM
Volume 19, Issue 3, Pages 272-279Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201700428
Keywords
annimycin; antimalarial activity; biosynthesis; dehydrotyrosine; mutagenesis; P450 monooxygenase
Funding
- China Scholarship Council
- Deutsche Forschungsgemeinschaft (DFG) [RTG 2202]
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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, annimycinB, which exhibited modest inhibitory activity against Plasmodium falciparum.
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