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Antimicrobial Agents and Chemotherapy, September 2003, p. 2823-2830, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2823-2830.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Deciphering Tuberactinomycin Biosynthesis: Isolation, Sequencing, and Annotation of the Viomycin Biosynthetic Gene Cluster

Michael G. Thomas,* Yolande A. Chan, and Sarah G. Ozanick

Department of Bacteriology, University of Wisconsin—Madison, Madison, Wisconsin 53706

Received 17 April 2003/ Returned for modification 19 May 2003/ Accepted 9 June 2003

The tuberactinomycin antibiotics are essential components in the drug arsenal against Mycobacterium tuberculosis infections and are specifically used for the treatment of multidrug-resistant tuberculosis. These antibiotics are also being investigated for their targeting of the catalytic RNAs involved in viral replication and for the treatment of bacterial infections caused by methicillin-resistant Staphylococcus aureus strains and vancomycin-resistant enterococci. We report on the isolation, sequencing, and annotation of the biosynthetic gene cluster for one member of this antibiotic family, viomycin, from Streptomyces sp. strain ATCC 11861. This is the first gene cluster for a member of the tuberactinomycin family of antibiotics sequenced, and the information gained can be extrapolated to all members of this family. The gene cluster covers 36.3 kb of DNA and encodes 20 open reading frames that we propose are involved in the biosynthesis, regulation, export, and activation of viomycin, in addition to self-resistance to the antibiotic. These results enable us to predict the metabolic logic of tuberactinomycin production and begin steps toward the combinatorial biosynthesis of these antibiotics to complement existing chemical modification techniques to produce novel tuberactinomycin derivatives.

* Corresponding author. Mailing address: Department of Bacteriology, University of Wisconsin—Madison, Rm. 304A E. B. Fred Hall, 1550 Linden Dr., Madison, WI 53706. Phone: (608) 263-9075 Fax: (608) 265-1492. E-mail: thomas{at}bact.wisc.edu.

Antimicrobial Agents and Chemotherapy, September 2003, p. 2823-2830, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2823-2830.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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