β-Branching in the biosynthesis of bongkrekic acid: a complex affair.

ABSTRACT: Bongkrekic acid is a potent respiratory toxin which inhibits the mitochondrial ATP/ADP carrier protein. The polyketide synthase that biosynthesises bongkrekic acid recruits a discrete cassette of β-branching enzymes (BonF-BonI) to install two distinct β-branches: an endo-β-methyl branch in module 1, and a carboxymethyl β-branch in module 11. Both β-branches contribute to specific interactions with bongkrekic acid's biological target. However, a critical component of the β-branching cassette, the donor acyl carrier protein (ACP_D), has not been identified in previous studies. Furthermore for the module 11 carboxymethyl β-branch to be retained, conversion to an endo-β-methyl branch via the enoyl-coenzyme A hydratase (ECH), BonI, must be avoided. The mechanistic

SUBMITTER: Hiseman MEM 

PROVIDER: S-EPMC12560621 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature