Switching the strict substrate specificities of the β-ketoacyl-acyl carrier protein synthases, FabH and BioZ.

ABSTRACT: The β-ketoacyl-acyl carrier protein (ACP) synthases are pivotal elongation enzymes that catalyze the condensation of acyl-CoA or acyl-ACP with malonyl-ACP to produce β-ketoacyl-ACP. Among these, the homologous enzymes FabH (β-ketoacyl-ACP synthase III) and the recently characterized BioZ play crucial roles, initiating the biosynthetic pathways for fatty acids and biotin, respectively. FabH primarily utilizes acetyl-CoA as the primer substrate, whereas BioZ exclusively condenses the longer glutaryl-CoA, which contains a charged ω-carboxyl group. Despite their similar catalytic mechanisms, the molecular bases for the strict substrate specificities remain undetermined. Here, we report crystal structures of the BioZ: glutaryl-CoA cocrystalized complexes and demonstrate the ability to swap the

SUBMITTER: Hang X 

PROVIDER: S-EPMC12625853 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature