Effects of Glycerol and Shikimic Acid on Rapamycin Production in Streptomyces rapamycinicus

Abstract

Rapamycin, derived from Streptomyces rapamycinicus, is an important bioactive compound having a therapeutic value in managing Parkinson’s disease, rheumatoid arthritis, cancer, and AIDS. Because of its pharmaceutical activity, studies over the past decade have focused on the biosynthesis of rapamycin to enhance its yield. In this study, the effect of rapG on rapamycin production was investigated. The rapG expression vector was constructed by utilizing the integration vector pSET152 under the control of the erythromycin resistance gene (ermE*), a strong constitutive promoter. The rapamycin yield of wild type (WT) and WT/ rapG overexpression mutant strains, under fermentation conditions, was analyzed by high-performance liquid chromatography (HPLC). Our results revealed that overexpression of rapG increased rapamycin production by approximately 4.9-fold (211.4 mg/l) in MD1 containing 15 g/l of glycerol, compared to that of the WT strain. It was also found that Illicium verum powder (10 g/l), containing shikimic acid, enhanced rapamycin production in both WT and WT/rapG strains. Moreover, the amount of rapamycin produced by the WT/rapG strain was statistically higher than that produced by the WT strain. In conclusion, the addition 15 g/l glycerol and 15 g/l I. verum powder produced the optimal conditions for rapamycin production by WT and WT/rapG strains.