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Licensed Unlicensed Requires Authentication Published by De Gruyter February 21, 2013

Biochemical characterization of an S-adenosyl-l-methionine-dependent methyltransferase (Rv0469) of Mycobacterium tuberculosis

  • Laxman S. Meena EMAIL logo , Puneet Chopra , Ram A. Vishwakarma and Yogendra Singh
From the journal Biological Chemistry


Tuberculostearic acid (l0-methylstearic acid, TSA) is a major constituent of mycobacterial membrane phospholipids, and its biosynthesis involves the direct methylation of oleic acid esterified as a component of phospholipids. The methyltransferases of mycobacteria were long proposed to be involved in the synthesis of methyl-branched short-chain fatty acids, but direct experimental evidence is still lacking. In this study, we identified the methyltransferase encoded by umaA in Mycobacterium tuberculosis H37Rv as a novel S-adenosyl-l-methionine (SAM)-dependent methyltransferase capable of catalyzing the conversion of olefinic double bond of phospholipid-linked oleic acid to biologically essential TSA. Therefore, UmaA, catalyzing such modifications, offer a viable target for chemotherapeutic intervention.

Corresponding author: Laxman S. Meena, CSIR-Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Mall Road, Delhi 110007, India

We thank Dr. Rajesh S. Gokhale, Director, CSIR-Institute of Genomics and Integrative Biology (IGIB), New Delhi, for making this work possible. One of the authors (L.S.M.) wants to thank the Department of Science and Technology (DST), for their financial support under the grant numbers GAP0050 and GAP0092, and the CSIR, for providing the funds under the In House Project Scheme (LSM59). The financial support was provided by NMITLI; CSIR is also acknowledged. P.C. was supported by the University Grant Commission, Delhi, India.


Akamatsu, Y. and Law, J.H. (1970). Enzymatic alkylenation of phospholipid fatty acid chains by extracts of Mycobacterium phlei. J. Biol. Chem. 245, 701–708.10.1016/S0021-9258(18)63319-8Search in Google Scholar

Ballou, C.E., Vilkas, E., and Lederer, E. (1963). Structural studies on the myo-inositol phospholipids of Mycobacterium tuberculosis (var. bovis, strain BCG). J. Biol. Chem. 238, 69–76.10.1016/S0021-9258(19)83963-7Search in Google Scholar

Besra, G.S., Morehouse, C.B., Rittner, C.M., Waechter, C.J., and Brennan, P.J. (1997). Biosynthesis of mycobacterial lipoarabinomannan. J. Biol. Chem. 272, 18460–18466.10.1074/jbc.272.29.18460Search in Google Scholar

Campbell, I.M. and Naworal, J. (1969). Composition of the saturated and monounsaturated fatty acids of Mycobacterium phlei. J. Lipid Res. 10, 593–598.10.1016/S0022-2275(20)43054-8Search in Google Scholar

Cole, S.T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S.V., Eiglmeier, K., Gas, S., Barry, C.E., et al. (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.10.1038/31159Search in Google Scholar

Dmitriev, B.A., Ehlers, S., Rietschel, E.T., and Brennan, P.J. (2000). Molecular mechanics of the mycobacterial cell wall: from horizontal layers to vertical scaffolds. J. Med. Microbiol. 290, 251–258.10.1016/S1438-4221(00)80122-8Search in Google Scholar

Glickman, M.S., Cahill, S.M., and Jacobs, W.R. Jr. (2000). The Mycobacterium tuberculosis cmaA2 gene encodes a mycolic acid trans-cyclopropane synthetase. J. Biol. Chem. 276, 2228–2233.10.1074/jbc.C000652200Search in Google Scholar PubMed

Goren, M.B. (1984). The mycobacteria: a sourcebook (New York: Marcel Dekker Inc.), pp. 379–415.Search in Google Scholar

Grzegorzewicz, A.E., Kordulakova, J., Jones, V., Born, S.E., Belardinelli, J.M., Vaquie, A., Gundi, V.A., Madacki, J., Slama, N., Laval, F., et al. (2012). A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone. J. Biol. Chem. 287, 38434–38441.10.1074/jbc.M112.400994Search in Google Scholar PubMed PubMed Central

Jackson, M., Crick, D.C., and Brennan, P.J. (2000). Phosphatidylinositol is an essential phospholipid of mycobacteria. J. Biol. Chem. 275, 30092–30099.10.1074/jbc.M004658200Search in Google Scholar PubMed

Laval, F., Haites, R., Movahedzadeh, F., Lemassu, A., Wong, C.Y., Stoker, N., Billman-Jacobe, H., and Daffe, M. (2008). Investigating the function of the putative mycolic acid methyltransferase UmaA: divergence between the Mycobacterium smegmatis and Mycobacterium tuberculosis proteins. J. Biol. Chem. 283, 1419–1427.10.1074/jbc.M708859200Search in Google Scholar PubMed

McAdam, R.A., Quan, S., Smith, D.A., Bardarov, S., Betts, J.C., Cook, F.C., Hooker, E.U., Lewis, A.P., Woollard, P., Everett, M.J., et al. (2002). Characterization of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 ORFs and mutants with altered virulence. Microbiology 148, 2975–2986.10.1099/00221287-148-10-2975Search in Google Scholar PubMed

Meena, L.S., Chopra, P., Bedwal, R.S., and Singh, Y. (2008). Cloning and characterization of a GTP binding protein from M. tuberculosis H37Rv. Enzyme Microb. Technol. 42, 138–144.10.1016/j.enzmictec.2007.08.008Search in Google Scholar PubMed

Meena, L.S., Dhakate, S.R., and Sahare, P.D. (2012). Elucidation of Mg2+ binding activity of adenylate kinase from Mycobacterium tuberculosis H37Rv using fluorescence studies. Biotechnol. Appl. Biochem. 59, 429–436.10.1002/bab.1043Search in Google Scholar PubMed

Nigou, J., Gilleron, M., Cahuzac, B., Bounery, J.D., Herold, M., Thurnher, M., and Puzo, G. (1997). The phosphatidyl-myo-inositol anchor of the lipoarabinomannans from Mycobacterium bovis bacillus Calmette-Guerin. Heterogeneity, structure, and role in the regulation of cytokine secretion. J. Biol. Chem. 272, 23094–23103.10.1074/jbc.272.37.23094Search in Google Scholar PubMed

Phetsuksiri, B., Jackson, M., Scherman, H., McNeil, M., Besra, G.S., Baulard, A.R., Slayden, R.A., DeBarber, A.E., Barry 3rd, C.E., Baird M.S., et al. (2003). Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis. J. Biol. Chem. 278, 53123–53130.10.1074/jbc.M311209200Search in Google Scholar PubMed PubMed Central

Takayama, K., Wang, C., and Besra, G.S. (2005). Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 18, 81–101.10.1128/CMR.18.1.81-101.2005Search in Google Scholar PubMed PubMed Central

Yuan, Y., Lee, R.E., Besra, G.S., Belisle, J.T., and Barry 3rd, C.E. (1995). Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 92, 6630–6634.10.1073/pnas.92.14.6630Search in Google Scholar PubMed PubMed Central

Yuan, Y., Mead, D., Schroeder, B.G., Zhu, Y., and Barry 3rd, C.E. (1998). The biosynthesis of mycolic acids in Mycobacterium tuberculosis. Enzymatic methyl(ene) transfer to acyl carrier protein bound meromycolic acid in vitro. J. Biol. Chem. 273, 21282–21290.10.1074/jbc.273.33.21282Search in Google Scholar PubMed

Received: 2013-1-23
Accepted: 2013-2-18
Published Online: 2013-2-21
Published in Print: 2013-7-1

©2013 by Walter de Gruyter Berlin Boston

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