Small molecule produced by Photorhabdus interferes with ubiquinone biosynthesis in Gram-negative bacteria.
Rachel BargabosAkira IinishiBryson A HawkinsThomas PrivalskyNorman PittSangkeun SonRachel CorsettiMichael F GatesRyan D MillerKim LewisPublished in: mBio (2024)
. DHB had previously been isolated from other bacterial species, but its mechanism of action remained unknown. We show that DHB is unique among antimicrobials, with dual action as an inhibitor of an important enzyme, UbiA, in the biosynthesis pathway of ubiquinone and as a prodrug. DHB is a mimic of the natural substrate, and UbiA modifies it into a toxic product, contributing to the antimicrobial action of this unusual antibiotic. We also uncover the mechanism of DHB selectivity, which depends on a particular fold of the UbiA enzyme.