Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing beta-oxo-mycolic acid analogs and accumulation of ketones.
Chem Biol
; 15(9): 930-9, 2008 Sep 22.
Article
en En
| MEDLINE
| ID: mdl-18804030
ABSTRACT
Mycolic acids are essential components of the mycobacterial cell wall. In this study, we show that a gene encoding a reductase involved in the final step of mycolic acid biosynthesis can be deleted in Mycobacterium smegmatis without affecting cell viability. Deletion of MSMEG4722 (ortholog of Mycobacterium tuberculosis Rv2509) altered culture characteristics and antibiotic sensitivity. The DeltaMSMEG4722 strain synthesized alpha-alkyl, beta-oxo intermediates of mycolic acids, which were found esterified to cell wall arabinogalactan. While the precursors could not be isolated directly due to their inherent instability during base treatment, their presence was established by prior reduction of the beta-oxo group by sodium borohydride. Interestingly, the mutant also accumulated unsaturated ketones, similar to tuberculenone from M. tuberculosis, which were shunt products derived from spontaneous decarboxylation of alpha-alkyl, beta-oxo fatty acid precursors of mycolic acids.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxidorreductasas
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Regulación Bacteriana de la Expresión Génica
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Pared Celular
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Cetonas
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Mycobacterium
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Ácidos Micólicos
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Año:
2008
Tipo del documento:
Article