伪-Methyl Acyl CoA Racemase Provides Mycobacterium tuberculosis Catabolic Access to Cholesterol Esters

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• 作者：Rui Lu ; Werner Schmitz ; Nicole S. Sampson
• 刊名：Biochemistry
• 出版年：2015
• 出版时间：September 22, 2015
• 年：2015
• 卷：54
• 期：37
• 页码：5669-5672
• 全文大小：213K
• ISSN：1520-4995

文摘

Metabolism of cholesterol by Mycobacterium tuberculosis (Mtb) contributes to its pathogenesis. We show that ChsE4-ChsE5 (Rv3504/Rv3505) specifically catalyzes dehydrogenation of the (25S)-3-oxo-cholest-4-en-26-oyl-CoA diastereomer in cholesterol side chain 尾-oxidation. Thus, a dichotomy between the supply of both 25R and 25S metabolic precursors by upstream cytochrome P450s and the substrate stereospecificity of ChsE4-ChsE5 exists. We reconcile the dilemma of 25R metabolite production by demonstrating that mycobacterial MCR (Rv1143) can efficiently epimerize C25 diastereomers of 3-oxo-cholest-4-en-26-oyl-CoA. Our data suggest that cholesterol and cholesterol ester precursors can converge into a single catabolic pathway, thus widening the metabolic niche in which Mtb survives.