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

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Article number102467
JournalCurrent Opinion in Chemical Biology
StatePublished - Jun 2024


  • Dinuclear/trinuclear iron enzyme
  • Metalloenzyme
  • Metallophore
  • Natural product biosynthesis
  • RiPPs

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry


Dive into the research topics of 'Multinuclear non-heme iron dependent oxidative enzymes (MNIOs) involved in unusual peptide modifications'. Together they form a unique fingerprint.

Cite this