earticle

영어

Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive and anti-cancer compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Especially TMC needed 100-fold lower concentrations than cyclosporine A as immunosuppressant. Previously, we isolated and characterized the entire TMC biosynthetic gene cluster from Streptomyces sp. CK4412.
Within the TMC biosynthetic gene cluster, we found and identified two putative hydroxylase genes, tmcG and tmcR, through in silico sequence comparison. TmcG was proposed as function of 3'-carbon hydroxyase, and tmcR was expected as 5-carbon oxygenase which modified TMC structure. Here we disrupted and over expressed tmcG, tmcR to understand each genes function. Moreover we constructed double knock-out mutant such as ΔtmcGΔtmcR. We found that those mutants produced novel TMC-like compounds through HPLC analysis. These modified compounds were shown different antifungal and protein phosphatase activity. The detailed result will be further discussed.