p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis

Stadthagen, Gustavo and Kordula´kova, Jana and Griffin, R. and Constant, Patricia and Bottova, Iveta and Barilone, Nathalie and Gicquel, Brigitte and Daffé, Mamadou and Jackson, Mary (2005) p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis. Journal of Biological Chemistry, 280 (49). 40699 -40706. ISSN 1083-351X

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (388kB) | Preview

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 glycolipidproducing 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 Km value for chorismate of 19.7Mandakcatvalueof0.102s1. 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 research was originally published in the Journal of Biological Chemistry. Gustavo Stadthagen, Jana Korduláková, Ruth Griffin, Patricia Constant, Iveta Bottová, Nathalie Barilone, Brigitte Gicquel, Mamadou Daffé, Mary Jackson. p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis. J. Biol. Chem. 2005; Vol 280, no 49 : 40699-4076. © 2005 the American Society for Biochemistry and Molecular Biology.
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences > Bacteriology
Identification Number: https://doi.org/10.1074/jbc.M508332200
Depositing User: Griffin, Ruth
Date Deposited: 13 Dec 2017 09:31
Last Modified: 14 Dec 2017 11:52
URI: http://eprints.nottingham.ac.uk/id/eprint/48706

Actions (Archive Staff Only)

Edit View Edit View