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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Functional characterization of ttmM unveils new tautomycin analogs and insight into tautomycin biosynthesis and
Jianhua Ju1, Wenli Li, Qiuping Yuan
1Division of Pharmaceutical Sciences, UW Paul P. Carbone Comprehensive Cancer Center Small Molecule Screening Facility, University of Wisconsin National Cooperative Drug Discovery Group, University of Wisconsin, Madison, Wisconsin 53705-2222, USA.
Abstract:
The biosynthetic gene cluster for tautomycin (TTM), a potent protein phosphatase (PP) inhibitor has recently been characterized. Inactivation of ttmM, which encodes a putative C3' hydroxylase, afforded mutant SB6005 which accumulated three new 3'-deshydroxy TTM analogs, supporting the function of TtmM and the previously proposed linear pathway for TTM biosynthesis. Bioassays reveal the importance of the C3' OH moiety in PP inhibition and that PP inhibition is not the exclusive mechanism driving TTM-induced cell death.
