New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity are Produced by Streptomyces asterosporus DSM 41452 and Its Mutant |
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| Authors: | Songya Zhang Jing Zhu Prof. Dr. David L. Zechel Dr. Claudia Jessen‐Trefzer Dr. Richard T. Eastman Dr. Thomas Paululat Prof. Dr. Andreas Bechthold |
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| Affiliation: | 1. Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg im Breisgau, Germany;2. Department of Chemistry, Queen's University, Kingston, Ontario, Canada;3. Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences/NIH, Rockville, MD, USA;4. Department of Chemistry and Biology, Universit?t Siegen, Siegen, Germany |
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| Abstract: | 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. |
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| Keywords: | annimycin antimalarial activity biosynthesis dehydrotyrosine mutagenesis P450 monooxygenase |
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