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Journal of Bacteriology, July 2004, p. 4051-4055, Vol. 186, No. 13
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.13.4051-4055.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Characterization of Mycobacterium smegmatis Expressing the Mycobacterium tuberculosis Fatty Acid Synthase I (fas1) Gene

Oren Zimhony,1,{dagger}* Catherine Vilchèze,2,{dagger} and William R. Jacobs Jr.2

Unit for Infectious Diseases, Kaplan Medical Center, The School of Medicine, Hebrew University, and Hadassah, Jerusalem, Israel,1 Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 104612

Received 10 February 2004/ Accepted 26 March 2004

Unlike most other bacteria, mycobacteria make fatty acids with the multidomain enzyme eukaryote-like fatty acid synthase I (FASI). Previous studies have demonstrated that the tuberculosis drug pyrazinamide and 5-chloro-pyrazinamide target FASI activity. Biochemical studies have revealed that in addition to C16:0, Mycobacterium tuberculosis FASI synthesizes C26:0 fatty acid, while the Mycobacterium smegmatis enzyme makes C24:0 fatty acid. In order to express M. tuberculosis FASI in a rapidly growing Mycobacterium and to characterize the M. tuberculosis FASI in vivo, we constructed an M. smegmatis {Delta}fas1 strain which contained the M. tuberculosis fas1 homologue. The M. smegmatis {Delta}fas1 (attB::M. tuberculosis fas1) strain grew more slowly than the parental M. smegmatis strain and was more susceptible to 5-chloro-pyrazinamide. Surprisingly, while the M. smegmatis {Delta}fas1 (attB::M. tuberculosis fas1) strain produced C26:0, it predominantly produced C24:0. These results suggest that the fatty acid elongation that produces C24:0 or C26:0 in vivo is due to a complex interaction among FASI, FabH, and FASII and possibly other systems and is not solely due to FASI elongation, as previously suggested by in vitro studies.

* Corresponding author. Mailing address: Unit for Infectious Diseases, Kaplan Medical Center, The School of Medicine, Hebrew University, and Hadassah, Rehovot 76100, Israel. Phone: 972-9441993. Fax: 972-8-9441866. E-mail: Oren_z{at}clalit.org.il.

{dagger} O.Z. and C.V. contributed equally to this work.

Journal of Bacteriology, July 2004, p. 4051-4055, Vol. 186, No. 13
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.13.4051-4055.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ngo, S. C., Zimhony, O., Chung, W. J., Sayahi, H., Jacobs, W. R. Jr., Welch, J. T. (2007). Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs. Antimicrob. Agents Chemother. 51: 2430-2435 [Abstract] [Full Text]  


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