Ancestral evolution of oxidase activity in a class of (S)-nicotine and (S)-6-hydroxynicotine-degrading flavoenzymes.

ABSTRACT: Reduced flavin cofactors have the innate ability to reduce molecular oxygen to hydrogen peroxide. Flavoprotein oxidases turbocharge the reaction of their flavin cofactor with oxygen, whereas flavoprotein dehydrogenases generally suppress it, yet our understanding of how these two enzyme classes control this reactivity remains incomplete. Here we used ancestral sequence reconstruction and biochemical characterization to retrace the evolution of oxidase activity in a lineage of nicotine/6-hydroxynicotine degrading enzymes of the flavoprotein amine oxidase superfamily. Our data suggest that the most ancient ancestor that gave rise to this lineage was a dehydrogenase, and that oxidase activity emerged later from within this group of dehydrogenases. We have identified the key amino acid replace

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC12272882 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature