CYPs and complex transformations in bacterial gibberellin phytohormone biosynthesis

Gibberellins (GAs) are structurally complex diterpenoids that serve as important hormones in plants, with crucial roles in growth and development, but also in modulating defense. Beyond their endogenous production by vascular plants, GAs also are produced by plant‐associated microbes, both fungi and bacteria. We have recently elucidated the biosynthetic pathway by which bacteria produce GA, revealing convergent evolution, yet striking similarities in the underlying (bio)chemical transformations. We are currently engaged in mechanistic studies of the cytochrome P450 monooxygenases CYP112 and CYP114, which catalyze particularly complex reactions. CYP112 carries out ring contraction, with extrusion of aldehyde, in a reaction that requires a dedicated ferredoxin, while CYP114 mediates a coupled demethylation and lactone ring forming transformation that requires multiple sequential reactions. We have carried out labeling studies to probe the catalyzed reactions, spectral binding studies to examine substrate specificity, and have solved crystal structures for both CYPs in the presence and absence of substrates/stable intermediates. Our most recent results will be discussed. Support or Funding Information This work was supported, in part, by grants from the NSF (CHE‐1609917) and NIH (GM131885).