Biochemical characterization of acyl-coenzyme A synthetases involved in mycobacterial steroid side-chain catabolism and molecular design: synthesis of an anti-mycobacterial agent.

ABSTRACT: The metabolism of host cholesterol by Mycobacterium tuberculosis is an important factor for both its virulence and pathogenesis. However, the rationale for this cholesterol metabolism has not been fully understood yet. In the present study, we characterized several previously undescribed acyl-CoA synthetases that are involved in the steroid side-chain degradation in Mycobacterium smegmatis, and an analogue of intermediate from steroid degradation, 5'-O-(lithocholoyl sulfamoyl) adenosine (LCA-AMS), was successfully designed and synthesized to be used as a specific anti-mycobacterial agent. The acyl-CoA synthetases exhibited strong preferences for the length of side chain. FadD19 homologs, including FadD19 (MSMEG_5914), FadD19-2 (MSMEG_2241), and FadD19-4 (MSMEG_3687), a

SUBMITTER: Niu Y 

PROVIDER: S-EPMC6453995 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature