Targeted activation and product identification of the type II polyketone gene cluster of Streptomyces cavourensis NA4

Abstract:

[Objective] To activate the silenced gene cluster for the biosynthesis of type II polyketides in Streptomyces cavourensis NA4 isolated from a marine environment, and identify the structure and antibacterial activity of the newly produced secondary metabolite. [Methods] The silenced or low-expressed biosynthetic gene cluster under laboratory culture conditions was activated by the addition of promoters and the knockout of negative regulator genes. The target compound was separated. The structure of the target compound was identified by electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). Furthermore, the antibacterial activity of the target compound was determined, and the biosynthetic pathway of the compound was deduced based on bioinformatics information. [Results] A biosynthetic gene cluster encoding type II polyketides was mined from the genome of S. cavourensis NA4 and successfully activated. A type II polyketide was separated from the expression products. The biosynthetic pathway of this compound was deduced and the antibacterial activity was determined. [Conclusion] Genome-oriented natural product mining can facilitate the separation of target products and fully tap the potential of Streptomyces in the production of secondary metabolites.