Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing β-oxo- mycolic acid analogs and accumulation of ketones

Bhatt, Apoorva, Brown, Alistair, Singh, Albel, Minnikin, David and Besra, Gurdyal (2008) Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing β-oxo- mycolic acid analogs and accumulation of ketones. Chemistry & Biology, 15 (9). pp. 930-939. ISSN 1074-5521

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Official URL: http://dx.doi.org/10.1016/j.chembiol.2008.07.007

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 ΔMSMEG4722 strain synthesized α-alkyl, β-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 β-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 α-alkyl, β-oxo fatty acid precursors of mycolic acids.

Item Type: Article
Uncontrolled Keywords: Mycobacteria, Ketones
Subjects: C100 Biology
F100 Chemistry
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: EPrint Services
Date Deposited: 19 Apr 2010 13:01
Last Modified: 27 Jun 2017 14:58
URI: http://nrl.northumbria.ac.uk/id/eprint/2723

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