This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mao, Y.
Right arrow Articles by Sherman, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mao, Y.
Right arrow Articles by Sherman, D. H.

 Previous Article  |  Next Article 

Journal of Bacteriology, April 1999, p. 2199-2208, Vol. 181, No. 7
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Genetic Localization and Molecular Characterization of Two Key Genes (mitAB) Required for Biosynthesis of the Antitumor Antibiotic Mitomycin C

Yingqing Mao, Mustafa Varoglu, and David H. Sherman*

Department of Microbiology and Biological Process Technology Institute, University of Minnesota, Minneapolis, Minnesota 55455

Received 3 November 1998/Accepted 12 January 1999

Mitomycin C (MC) is an antitumor antibiotic derived biosynthetically from 3-amino-5-hydroxybenzoic acid (AHBA), D-glucosamine, and carbamoyl phosphate. A gene (mitA) involved in synthesis of AHBA has been identified and found to be linked to the MC resistance locus, mrd, in Streptomyces lavendulae. Nucleotide sequence analysis showed that mitA encodes a 388-amino-acid protein that has 71% identity (80% similarity) with the rifamycin AHBA synthase from Amycolatopsis mediterranei, as well as with two additional AHBA synthases from related ansamycin antibiotic-producing microorganisms. Gene disruption and site-directed mutagenesis of the S. lavendulae chromosomal copy of mitA completely blocked the production of MC. The function of mitA was confirmed by complementation of an S. lavendulae strain containing a K191A mutation in MitA with AHBA. A second gene (mitB) encoding a 272-amino-acid protein (related to a group of glycosyltransferases) was identified immediately downstream of mitA that upon disruption resulted in abrogation of MC synthesis. This work has localized a cluster of key genes that mediate assembly of the unique mitosane class of natural products.

* Corresponding author. Mailing address: Department of Microbiology, Box 196 UFHC, 1460 Mayo Memorial Building, 420 Delaware St. SE, Minneapolis, MN 55455-0312. Phone: (612) 626-0199. Fax: (612) 624-6641. E-mail: david-s{at}biosci.umn.edu.

Journal of Bacteriology, April 1999, p. 2199-2208, Vol. 181, No. 7
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sitachitta, N., Lopanik, N. B., Mao, Y., Sherman, D. H. (2007). Analysis of a Parallel Branch in the Mitomycin Biosynthetic Pathway Involving the mitN-Encoded Aziridine N-Methyltransferase. J. Biol. Chem. 282: 20941-20947 [Abstract] [Full Text]  
  • Jensen, P. R., Williams, P. G., Oh, D.-C., Zeigler, L., Fenical, W. (2007). Species-Specific Secondary Metabolite Production in Marine Actinomycetes of the Genus Salinispora. Appl. Environ. Microbiol. 73: 1146-1152 [Abstract] [Full Text]  
  • Sheldon, P. J., Mao, Y., He, M., Sherman, D. H. (1999). Mitomycin Resistance in Streptomyces lavendulae Includes a Novel Drug-Binding-Protein-Dependent Export System. J. Bacteriol. 181: 2507-2512 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»