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J. Biol. Chem., Vol. 276, Issue 20, 16833-16839, May 18, 2001
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From the Multidrug-resistant tuberculosis is a major
global health emergency. Cell wall lipids of Mycobacterium
tuberculosis can play crucial roles in the pathogenesis. The
enzymes involved in their synthesis can be ideal new drug targets
against tuberculosis, because many such lipids are unique to this
pathogen. A variety of multiple methyl-branched fatty acids are among
such unique lipids. We have identified seven genes highly homologous to
the mas gene, which is known to be involved in the
production of one class of such multiple methyl-branched fatty acids.
One of these mas-like genes, pks2, was
disrupted using a phage-mediated delivery of the disruption construct.
Gene disruption by homologous recombination was confirmed by polymerase
chain reaction analysis of the flanking regions of the introduced
disrupted gene and by Southern analysis. Thin-layer and radio
gas-chromatographic analyses of lipids derived from
[1-14C]propionic acid and gas chromatography/mass
spectrometry analysis of the fatty acids and hydroxy fatty acids showed
that the pks2 mutant was incapable of producing hepta- and
octamethyl phthioceranic acids and hydroxyphthioceranic acids that are
the major acyl constituents of sulfolipids. Consequently,
pks2 mutant does not produce sulfolipids. Sulfolipid
deficiency in pks2 mutant was confirmed by two-dimensional thin-layer chromatographic analysis of lipids derived from
[1-14C]propionic acid and
35SO
The Mycobacterium tuberculosis pks2 Gene Encodes the
Synthase for the Hepta- and Octamethyl-branched Fatty Acids Required
for Sulfolipid Synthesis*
§¶,§¶,§¶,§¶
Neurobiotechnology Center and Departments of
§ Biochemistry and ¶ Molecular and Cellular
Biochemistry, The Ohio State University, Columbus, Ohio 43210
*
This work was supported in part by Grants AI46582 and
AI35272 from the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Neurobiotechnology
Center, Rightmire Hall, 1060 Carmack Rd., The Ohio State University, Columbus, OH 43210. Tel.: 614-292-5682; Fax: 614-292-5379; E-mail: Kolattukudy.2@osu.edu.
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