Exploration and biosynthetic mechanism analysis of elaiophylin and actinopyranone from Streptomyces albus DSM 41398

Abstract:

[Objective] The targeted type I polyketide-derived compounds was explored to discover diverse compounds with good biological activity from Streptomyces albus DSM 41398. The biosynthetic pathways of the isolates were further elucidated based on the structure determination and bioinformatics analysis. [Methods] The target compounds were discovered based on comparative HPLC analysis of the fermented broths of wild type and type I PKS gene cluster inactivated mutants. Their chemical structures were elucidated based on ¹H-,¹³C-NMR and HR-ESI-MS. Additionally, their biosynthetic pathways were illuminated by bioinformatics analysis. [Results] Two type I polyketide-originated compounds with antitumor activity, elaiophilin and actinopyranone, were isolated from 5 L fermented broth of S. albus DSM 41398. Their gene clusters were located, and the biosynthetic pathways were proposed, respectively. Notably, the biosynthesis gene cluster of actinopyranone was reported for the first time in this study. [Conclusion] The investigation of elaiophilin and actinopyranone not only offered a strategy to discover type I polyketide compounds through genome mining, but also paved ways for further compound structural modifications.