Pyridoxal phosphate-dependent reactions in natural products biosynthesis

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are widespread in nature. Most reactions catalyzed by PLP-dependent enzymes traverse through a carbanionic intermediate, which is stabilized by the PLP cofactor. Like all enzymes that deal with carbanions, PLP-dependent enzymes can be subject to reaction with electrophiles like O2 . However, the majority reactions of PLP-dependent enzymes with O2 are paracatalytic. Recent studies have identified PLP-dependent enzymes that employ O2 as a co-substrate for oxidation of arginine. Such enzymes are part of biosynthetic pathways that convert arginine into heterocycle-containing natural products. In this talk, I will discuss the discovery of these arginine oxidases, and I will describe what we have learned about their mechanisms. I will furthermore highlight how we characterized an O2 -, PLP-dependent enzyme encoded by an unknown gene cluster and then used this discovery as a starting point to reconstitute the biosynthetic pathway to the antibiotic azomycin. © FASEB.