Engineering of Streptomyces platensis MA7339 for Overproduction of Platencin and Congeners

Platensimycin (1) and platencin (2) are novel antibiotic leads against multidrug resistant pathogens. The production of 2 in Streptomyces platensis MA7339 is under the control of ptnR1, a GntR-like transcriptional regulator. Inactivating ptnR1 afforded S. platensis MA7339 mutant strain SB12600 that overproduces 2 at a titer similar to 100-fold greater than that from the wild-type strain and accumulates platencin A(1) (3) and eight new congeners, platencins A(2)-A(9) (4-11). The isolation, structural elucidation, and antibacterial activity of 4-11, in comparison to 1-3, are described.