p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis

Stadthagen, Gustavo, Kordulakova, Jana, Griffin, Ruth, Constant, Patricia, Bottova, Ivetta, Barilone, Nathalie, Gicquel, Brigitte, Daffe, Mamadou and Jackson, Mary (2005) p-Hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. The Journal of Biological Chemistry, 280(49), pp. 40699-40706. ISSN (print) 0021-9258

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Abstract

Glycosylated p-hydroxybenzoic acid methyl esters and structurally related phenolphthiocerol glycolipids are important virulence factors of Mycobacterium tuberculosis. Although both types of molecules are thought to be derived from p-hydroxybenzoic acid, the origin of this putative biosynthetic precursor in mycobacteria remained to be established. We describe the characterization of a transposon mutant of M. tuberculosis deficient in the production of all forms of p-hydroxybenzoic acid derivatives. The transposon was found to be inserted in Rv2949c, a gene located in the vicinity of the polyketide synthase gene pks15/1, involved in the elongation of p-hydroxybenzoate to phenolphthiocerol in phenolic glycolipid-producing strains. A recombinant form of the Rv2949c enzyme was produced in the fast-growing non-pathogenic Mycobacterium smegmatis and purified to near homogeneity. The recombinant enzyme catalyzed the removal of the pyruvyl moiety of chorismate to form p-hydroxybenzoate with an apparent K(m) value for chorismate of 19.7 microm and a k(cat) value of 0.102 s(-1). Strong inhibition of the reaction by p-hydroxybenzoate but not by pyruvate was observed. These results establish Rv2949c as a chorismate pyruvate-lyase responsible for the direct conversion of chorismate to p-hydroxybenzoate and identify Rv2949c as the sole enzymatic source of p-hydroxybenzoic acid in M. tuberculosis.

Item Type: Article
Additional Information: This work was supported by the Institut Pasteur, the European Commission, within the 6th Framework Program contract number LSHP-CT-2003-503367, the Heiser Program for Research in Leprosy and Tuberculosis, the CONACyT program from Mexico, and the Marie Curie Training Site program number CT-2000-00058 from the European Commission.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017)
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Depositing User: Ruth Griffin
Date Deposited: 08 Jul 2016 08:20
Last Modified: 08 Jul 2016 08:20
DOI: https://doi.org/10.1074/jbc.M508332200
URI: http://eprints.kingston.ac.uk/id/eprint/33834

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