Inhibition of de novo fatty acid synthesis in Mycobacterium tuberculosis.

ABSTRACT: De novo fatty acid synthesis produces the acyl units needed to generate phospholipids, lipoproteins, enzyme prosthetic factors, polyketides, and mycolic acids in mycobacterium tuberculosis (Mtb). Here, we identified sALT629, a butoxyphenyl-tetrazole-acetamide compound that inhibits de novo lipid synthesis in Mtb. This compound disrupts the Mtb lipidome and prevents incorporation of metabolic tracers into acyl chains of Mtb lipids. Unexpectedly, we also found that sALT629 treatment significantly depleted triacylglycerol (TAG) pools as a metabolic compensation mechanism when de novo fatty acid synthesis was inhibited. Resistance to sALT629 was mediated by loss of function mutations in HadC, the non-essential hydroxyacyl- acyl carrier protein -dehydratase subunit involved in the synthesis of

SUBMITTER: Roszkowski EK 

PROVIDER: S-EPMC12803843 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature