Multinuclear non-heme iron dependent oxidative enzymes (MNIOs) involved in unusual peptide modifications.

Multinuclear non-heme iron dependent oxidative enzymes (MNIOs), formerly known as domain of unknown function 692 (DUF692), are involved in the post-translational modification of peptides during the biosynthesis of peptide-based natural products. These enzymes catalyze highly unusual and diverse chemical modifications. Several class-defining features of this large family (>14 000 members) are beginning to emerge. Structurally, the enzymes are characterized by a TIM-barrel fold and a set of conserved residues for a di- or tri–iron binding site. They use molecular oxygen to modify peptide substrates, often in a four-electron oxidation taking place at a cysteine residue. This review summarizes the current understanding of MNIOs. Four modifications are discussed in detail: oxazolone-thioamide formation, β-carbon excision, hydantoin-macrocycle formation, and 5-thiooxazole formation. Briefly discussed are two other reactions that do not take place on Cys residues. [Display omitted] • Remarkable chemistry catalyzed by multinuclear non-heme iron-dependent oxidative enzymes (MNIOs). • MNIOs convert Cys to an oxazolone-thioamide in methanobactin biosynthesis and to 5-thiooxazole in bufferin biosynthesis. • MNIOs excise the β-carbon of Cys in 3-thiaglutamate biosynthesis. • MNIOs convert Cys residues into macrocyclic thioaminals and hydantoins. • MNIOs cleave the peptide backbone at Asn to give a C-terminal amide and convert a C-terminal Asp into aminopyruvic acid. [ABSTRACT FROM AUTHOR]