Academic Journal
p-hydroxybenzoic acid synthesis in Mycobacterium tuberculosis.
| العنوان: | p-hydroxybenzoic acid synthesis in Mycobacterium tuberculosis. |
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| المؤلفون: | Stadthagen, G., Korduláková, J., Griffin, R., Constant, P., Bottová, I., Barilone, Nathalie, Gicquel, B., Daffé, M., Jackson, M. |
| المساهمون: | Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur Paris (IP), National Institute for Medical Research (NIMR), Medical Research Council, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0021-9258. |
| بيانات النشر: | HAL CCSD American Society for Biochemistry and Molecular Biology |
| سنة النشر: | 2005 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: Chorismic Acid, MESH: DNA Transposable Elements, MESH: Polyketide Synthases, MESH: Pyruvic Acid, MESH: Recombinant Proteins, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, MESH: Escherichia coli, MESH: Methylation, MESH: Mutation, MESH: Mycobacterium smegmatis, MESH: Mycobacterium tuberculosis, MESH: Oxo-Acid-Lyases, MESH: Parabens, MESH: Phenotype, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] |
| الوصف: | 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 Km value for chorismate of 19.7 μm and a kcat 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/16210318; hal-00078841; https://hal.science/hal-00078841; https://hal.science/hal-00078841/document; https://hal.science/hal-00078841/file/PIIS0021925820590364.pdf; PUBMED: 16210318 |
| DOI: | 10.1074/jbc.m508332200 |
| الاتاحة: | https://hal.science/hal-00078841 https://hal.science/hal-00078841/document https://hal.science/hal-00078841/file/PIIS0021925820590364.pdf https://doi.org/10.1074/jbc.m508332200 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.65254057 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.m508332200 |
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