Improvement of platensimycin and platencin production and their activities against clinical methicillin-resistant Staphylococcus aureus isolates in China

Platensimycin (PTM) and platencin (PTN), isolated from several strains of Streptomyces platensis, are potent antibiotics against multi-drug resistant bacteria. Recently, PTM was also reported to have antidiabetic and antisteatotic effects in mouse models. Through a novel genome-mining method, we have identified six PTM and PTN dual-producing strains. By inactivation of pathway-specific transcriptional repressor gene ptmR1, we then generated three mutant strains which can over-produce PTM or PTN, with a yield of 0.3 g/L by fermentation. In this study, we report the improvement of PTM and PTN fermentation and isolation methods, as well as their activities against clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates in China.

Fermentation medium optimization was achieved by manipulation of medium carbon and nitrogen sources, as well as inorganic salts. The yield of PTM could increase to over 1 g/L in both 250-mL shaking flasks and 15-L fermentors, which was significantly higher comparing to the yield in the previous medium. A polyamide chromatography step was included for PTM or PTN purification, which eliminated the HPLC purification and thus greatly reduced the time and cost to purify gram-scale of both compounds. Finally, the purified PTM and PTN were both tested against clinical isolates of MRSA strains in China and their activities were reported.