Gustavo Stadthagen
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
Authors
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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Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
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