NTF2‐Like Enzymes as Versatile Biocatalysts in Fungal Natural Product Biosynthesis

Abstract Fungal natural products (NPs), known for their potent bioactivities, can be utilized as human therapeutics and agrochemicals. These bioactive and structurally complex compounds are biosynthesized through condensation of monomeric building blocks to construct core scaffolds, followed by various modification steps. Recent studies have revealed that a unique class of enzymes from the NTF2‐like protein family plays important roles in the biosynthesis of complex fungal NPs. These NTF2‐like enzymes belong to a large group of related proteins that share a common fold with nuclear transport factor 2, and are capable of catalyzing various reactions. In this study, we summarize the recent progress in discovering and characterizing the catalytic functions of fungal‐derived NTF2‐like enzymes, including dehydratases, epimerases, isomerases, semipinacolases, pericyclases, and aldolases. These findings not only provide valuable insights into new catalytic reactions and mechanisms, but also offer opportunities to discover novel NPs and biocatalysts through genome mining.