LAUSR

Pyrazines are widespread chemical compounds that include pheromones and odors. Herein, a novel mechanism used by Pseudomonas fluorescens SBW25 to biosynthesize monocyclic pyrazines is reported. Heterologous expression of the papABC genes that synthesize the natural α‐amino acid 4‐aminophenylalanine (4APhe), together with three adjacent papDEF genes of unknown function, in Escherichia coli resulted in the production of 2,5‐dimethyl‐3,6‐bis(4‐aminobenzyl)pyrazine (DMBAP), which comprised two symmetrical aminobenzyl moieties derived from 4APhe. It is found that PapD is a novel amino acid C‐acetyltransferase, which decarboxylates and transfers acetyl residues to 4APhe, to generate an α‐aminoketone, which spontaneously dehydrates and condenses to give dihydro DMBAP. PapF is a novel oxidase in the amine oxidase superfamily that oxidizes dihydro DMBAP to yield the pyrazine ring of DMBAP. These two enzymes constitute a unique mechanism for synthesizing monocyclic pyrazines and might serve as a novel strategy for the enzymatic synthesis of pyrazine derivatives from natural α‐amino acids.