<jats:title>Abstract</jats:title><jats:p>In this study, we report that <jats:italic>Streptomyces asterosporus</jats:italic> DSM 41452 is a producer of new molecules related to the nonribosomal cyclodepsipeptide WS9326A and the polyketide annimycin. <jats:italic>S. asterosporus</jats:italic> 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 <jats:italic>S. asterosporus</jats:italic> 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 <jats:italic>sas16</jats:italic> encoding a cytochrome P450 monooxygenase was involved in the synthesis of the novel (<jats:italic>E</jats:italic>)‐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 <jats:italic>Plasmodium falciparum</jats:italic>.