1887

Abstract

Mycolic acids are vital components of the cell wall and are essential for survival. While most components of the fatty acid synthase-II (FAS-II) enzymic machinery that synthesizes these long chain -alkyl, -hydroxy fatty acids have been identified, the gene encoding the -hydroxyacyl-acyl carrier protein (ACP) dehydratase activity has remained elusive. Recent bioinformatics-based studies and drug inhibition experiments have identified the gene as a promising candidate for this role. Using a recently described, specialized transduction-based genetic tool we now demonstrate that , the homologue of , is an essential gene; null mutants of the gene could only be generated in a merodiploid strain which contained a second integrated acetamide-inducible copy of . Growth of the conditional mutant in the absence of acetamide resulted in loss of mycolic acid biosynthesis and eventually loss of viability due to cell lysis. Null mutants could also be generated in a strain containing an integrated copy of , indicating that was the functional counterpart of in . Our results demonstrate that is an essential gene involved in mycolic acid biosynthesis and encodes the FAS-II -hydroxyacyl-ACP dehydratase.

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2007-12-01
2019-10-17
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