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

Biochemistry
Rui LuNicole S Sampson

Abstract

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 β-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.

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Citations

Feb 2, 2016·Bioorganic & Medicinal Chemistry·Ashley N WercholukWilliam E Allen
May 11, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia WrońskaKatarzyna Lisowska
Dec 22, 2016·British Journal of Pharmacology·Areej Abuhammad
May 3, 2018·Pathogens and Disease·Kaley M WilburnBrian C VanderVen

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