Division of Pharmaceutical Sciences,1 University of Wisconsin National Cooperative Drug Discovery Group,2 Department of Chemistry, University of WisconsinMadison, Madison, Wisconsin 53705,3 Antibiotics Laboratory, Discovery Research Institute, RIKEN, Wako 351-0198, Japan4
Received 1 February 2006/ Accepted 13 March 2006
Tautomycin (TTM), a potent protein phosphatase inhibitor, consists of a polyketide chain containing a spiroketal moiety and an acyl chain bearing a dialkylmaleic anhydride structure. PCR using degenerate primers was used to clone genes from Streptomyces spiroverticillatus for formation of the methoxymalonyl-acyl carrier protein. This locus was found to contain five genes (ttmC, ttmA, ttmD, ttmB, and ttmE), one of which was used as a probe to clone the 110-kb TTM biosynthetic gene cluster. The involvement of the ttmA gene in TTM biosynthesis was confirmed by gene inactivation and mutation complementation experiments.
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