earticle

영어

The entire biosynthetic gene cluster for Tautomycetin (TMC), a potent T-cell immunosuppressive compound that are superior to cyclosporine A both in vitro and in vivo. TMC produced by soil microorganism Streptomyces sp. CK4412 has earlier been investigated, cloned and sequenced[1]. TMC has a unique structure, containing an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Here we propose two putative genes which participate a pathway to synthesize both dialkylmaleic anhydride moiety and terminal alkene as dehydratase enzyme. Within the TMC biosynthetic gene cluster, we found two putative dehydratase enzyme tmcM and tmcQ. A 1.5Kb gene tmcM and 1.4kb gene tmcQ both are located downstream of the PKS tmcB gene. In silico database comparisons revealed that TmcM function as L-carnitine dehydratase and another putative dehydratase enzyme TmcQ is a member of the MmgE/PrpD protein family. New TMC analogues characterized from inactivation of two genes, tmcM and tmcQ in Streptomyces sp. CK4412, resulting from this it constructed mutant strains △tmcM and △tmcQ respectively. The importance of the function by TmcM and TmcQ will be further studied.