Details

Autor(en) / Beteiligte

• Zhang, Songya
• Zhu, Jing
• Zechel, David L.
• Jessen‐Trefzer, Claudia
• Eastman, Richard T.
• Paululat, Thomas
• Bechthold, Andreas

Titel

New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity are Produced by Streptomyces asterosporus DSM 41452 and Its Mutant

Ist Teil von

• Chembiochem : a European journal of chemical biology, 2018-02, Vol.19 (3), p.272-279

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. The WS9326A biosynthetic gene cluster in S. asterosporus DSM 41452 is identified through bioinformatic analysis and mutagenesis. Analysis of the cluster reveals the SAS16 gene encoding a cytochrome P450 monooxygenase that is involved in the biosynthesis of the (E)‐2,3‐dehydrotyrosine residue in WS9326As. Surprisingly, one mutant of S. asterosporus DSM 41452 produces a new annimycin derivative with antimalarial activity.