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Journal of Bacteriology, June 2006, p. 4148-4152, Vol. 188, No. 11
0021-9193/06/$08.00+0     doi:10.1128/JB.00172-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Utilization of the Methoxymalonyl-Acyl Carrier Protein Biosynthesis Locus for Cloning of the Tautomycin Biosynthetic Gene Cluster from Streptomyces spiroverticillatus

Wenli Li,1 Jianhua Ju,1 Hiroyuki Osada,4 and Ben Shen1,2,3*

Division of Pharmaceutical Sciences,1 University of Wisconsin National Cooperative Drug Discovery Group,2 Department of Chemistry, University of Wisconsin—Madison, 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.

* Corresponding author. Mailing address: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin—Madison, 777 Highland Ave., Madison, WI 53705. Phone: (608) 263-2673. Fax: (608) 262-5345. E-mail: bshen{at}pharmacy.wisc.edu.

Journal of Bacteriology, June 2006, p. 4148-4152, Vol. 188, No. 11
0021-9193/06/$08.00+0     doi:10.1128/JB.00172-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, W., Ju, J., Rajski, S. R., Osada, H., Shen, B. (2008). Characterization of the Tautomycin Biosynthetic Gene Cluster from Streptomyces spiroverticillatus Unveiling New Insights into Dialkylmaleic Anhydride and Polyketide Biosynthesis. J. Biol. Chem. 283: 28607-28617 [Abstract] [Full Text]  
  • Choi, S.-S., Hur, Y.-A., Sherman, D. H., Kim, E.-S. (2007). Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412. Microbiology 153: 1095-1102 [Abstract] [Full Text]  


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