Utilization of the methoxymalonyl-acyl carrier protein biosynthesis locus for cloning of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatus.
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.
Li
Wenli
W
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI 53705, USA.
Ju
Jianhua
J
Osada
Hiroyuki
H
Shen
Ben
B
D000213:Acyl Carrier Protein / Q000378:metabolism*; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D005816:Genetic Complementation Test; D005810:Multigene Family; D011714:Pyrans / Q000378:metabolism*; D013141:Spiro Compounds / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D000213:Acyl Carrier Protein; D004269:DNA, Bacterial; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin