Genome sequencing allows a rapid and efficient identification of novel catalysts that produce novel secondary metabolites. Here we describe the catalytic properties of dihydropyrone synthase A (DpyA), a novel type III polyketide synthase encoded in a linear plasmid of Streptomyces reveromyceticus. Heterologous expression of dpyA led to the accumulation of alkyldihydropyrones A (1), B (2), C (3) and D (4), which are novel dihydropyran compounds that exhibit weak cytotoxicity against the leukemia cell line HL-60. DpyA catalyzes the condensation of β-hydroxyl acid thioester and methylmalonyl-CoA to yield a triketide intermediate that then undergoes lactonization of a secondary alcohol and a thioester to give alkyldihydropyrone.
ASJC Scopus subject areas
- Drug Discovery