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Deletion of a mycobacterial gene encoding a reductase leads to an altered cell wall containing β-oxo-mycolic acid analogues, and the accumulation of longchain ketones related to mycolic acids.

Bhatt, Apoorva and Brown, Alistair K. and Singh, Albel and Minnikin, David E and Besra, Gurdyal S (2008) Deletion of a mycobacterial gene encoding a reductase leads to an altered cell wall containing β-oxo-mycolic acid analogues, and the accumulation of longchain ketones related to mycolic acids. Chemistry and Biology, 15 (9). pp. 930-939. ISSN 1074-5521

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URL of Published Version: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRP-4TGGYY4-9&_user=122868&_coverDate=09%2F22%2F2008&_alid=795926211&_rdoc=1&_fmt=high&_orig=search&_cdi=6240&_sort=d&_docanchor=&view=c&_ct=2&_acct=C000010083&_version=1&_urlVersion=0&_userid=122

Identification Number/DOI: doi:10.1016/j.chembiol.2008.07.007

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.

Type of Work:Article
Date:19 September 2008 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QP Physiology
Institution:University of Birmingham
Copyright Holders:Cell Press
ID Code:101
Refereed:YES
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