Fungal RiPPs Side Chain Macrocyclization Catalyzed by Copper-Dependent DUF3328 Enzyme
Chen‐Yu Chiang, Masao Ōhashi, Yi Tang
Abstract
Fungal enzymes containing domain of unknown function (DUF) 3328 have been implicated in the oxidative maturation of ribosomally synthesized and post-translationally modified peptides (RiPPs). We report here the functional characterization of one such enzyme, AprY, involved in the biosynthesis of RiPP asperipin-2a. Biochemical reconstitution of AprY showed the enzyme catalyzes two consecutive C-O cross-linking reactions between tyrosines and beta-carbons of residues in the core hexapeptide. The side-chain macrocyclization activities of AprY are copper- and oxygen-dependent and do not require a leader peptide sequence.
Topics & Concepts
ChemistrySide chainEnzymeCopperCatalysisCombinatorial chemistryChain (unit)StereochemistryBiochemistryOrganic chemistryAstronomyPolymerPhysicsMicrobial Natural Products and BiosynthesisEnzyme Catalysis and ImmobilizationEnzyme-mediated dye degradation