Heterologous Expression of a Cryptic Giant Type I PKS Gene Cluster Leads to the Production of Ansaseomycin

Genome mining of the marine Streptomyces seoulensis A01 enabled the identification of a giant type I polyketide synthase gene cluster (asm). Heterologous expression of the cryptic asm cluster using a bacterial artificial chromosome vector in heterologous host led to the production of ansaseomycins A (1) and B (2). A plausible biosynthetic pathway was also proposed. Additionally, compounds 1 and 2 are active against K562 cell lines with IC50 values of 13.3 and 18.1 mu M, respectively.