OXSM

OXSM (3-oxoacyl-ACP synthase, mitochondrial), also termed mitochondrial β-ketoacyl-ACP synthase or KAS, is a key enzyme in mitochondrial fatty acid synthesis (mtFAS). It catalyzes the condensation of malonyl-ACP with acyl-ACP intermediates to elongate fatty acid chains, a critical step for generating lipoic acid precursors and maintaining functional mitochondrial acetyl-CoA pools. OXSM operates within the mtFAS pathway, which intersects with energy metabolism, iron-sulfur cluster biogenesis, and mitochondrial membrane integrity. Dysregulation of OXSM has been linked to metabolic disorders, including insulin resistance and non-alcoholic fatty liver disease (NAFLD), as well as rare mitochondrial encephalopathies. Recent studies implicate OXSM in cancer cell survival via lipid metabolism reprogramming. While no direct OXSM-targeted therapies exist, small-molecule inhibitors of bacterial homologs (e.g., FabH in pathogens) inform drug discovery efforts. Pharmacological modulation of mtFAS is being explored for metabolic syndrome and oncology applications, with OXSM emerging as a potential node for precision metabolic interventions.