p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis
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 precu...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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American Society for Biochemistry and Molecular Biology
2005
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| Online Access: | https://eprints.nottingham.ac.uk/48706/ |
| _version_ | 1848797828769382400 |
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| author | Stadthagen, Gustavo Kordula´kova, Jana Griffin, R. Constant, Patricia Bottova, Iveta Barilone, Nathalie Gicquel, Brigitte Daffé, Mamadou Jackson, Mary |
| author_facet | Stadthagen, Gustavo Kordula´kova, Jana Griffin, R. Constant, Patricia Bottova, Iveta Barilone, Nathalie Gicquel, Brigitte Daffé, Mamadou Jackson, Mary |
| author_sort | Stadthagen, Gustavo |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:10:05Z |
| format | Article |
| id | nottingham-48706 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:10:05Z |
| publishDate | 2005 |
| publisher | American Society for Biochemistry and Molecular Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-487062020-05-04T16:26:16Z https://eprints.nottingham.ac.uk/48706/ p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis Stadthagen, Gustavo Kordula´kova, Jana Griffin, R. Constant, Patricia Bottova, Iveta Barilone, Nathalie Gicquel, Brigitte Daffé, Mamadou Jackson, Mary 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. American Society for Biochemistry and Molecular Biology 2005-12-09 Article PeerReviewed Stadthagen, Gustavo, Kordula´kova, Jana, Griffin, R., Constant, Patricia, Bottova, Iveta, Barilone, Nathalie, Gicquel, Brigitte, Daffé, Mamadou and Jackson, Mary (2005) p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis. Journal of Biological Chemistry, 280 (49). 40699 -40706. ISSN 1083-351X http://www.jbc.org/content/280/49/40699 doi:10.1074/jbc.M508332200 doi:10.1074/jbc.M508332200 |
| spellingShingle | Stadthagen, Gustavo Kordula´kova, Jana Griffin, R. Constant, Patricia Bottova, Iveta Barilone, Nathalie Gicquel, Brigitte Daffé, Mamadou Jackson, Mary p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title | p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title_full | p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title_fullStr | p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title_full_unstemmed | p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title_short | p-Hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| title_sort | p-hydroxybenzoic acid synthesis in mycobacterium tuberculosis |
| url | https://eprints.nottingham.ac.uk/48706/ https://eprints.nottingham.ac.uk/48706/ https://eprints.nottingham.ac.uk/48706/ |