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p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis

Stadthagen, Gustavo; Kordula�kova, Jana; Griffin, R.; Constant, Patricia; Bottova, Iveta; Barilone, Nathalie; Gicquel, Brigitte; Daff�, Mamadou; Jackson, Mary

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Authors

Gustavo Stadthagen

Jana Kordula�kova

RUTH GRIFFIN Ruth.Griffin1@nottingham.ac.uk
Assistant Professor

Patricia Constant

Iveta Bottova

Nathalie Barilone

Brigitte Gicquel

Mamadou Daff�

Mary Jackson



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.

Citation

Stadthagen, G., Kordula´kova, J., Griffin, R., Constant, P., Bottova, I., Barilone, N., Gicquel, B., Daffé, M., & Jackson, M. (2005). p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis. Journal of Biological Chemistry, 280(49), https://doi.org/10.1074/jbc.M508332200

Journal Article Type Article
Acceptance Date Oct 6, 2005
Publication Date Dec 9, 2005
Deposit Date Dec 13, 2017
Publicly Available Date Dec 13, 2017
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 280
Issue 49
DOI https://doi.org/10.1074/jbc.M508332200
Public URL https://nottingham-repository.worktribe.com/output/703505
Publisher URL http://www.jbc.org/content/280/49/40699
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.
Contract Date Dec 13, 2017

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