TY - JOUR
T1 - Multinuclear non-heme iron dependent oxidative enzymes (MNIOs) involved in unusual peptide modifications
AU - Chen, Jeff Y.
AU - van der Donk, Wilfred A.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - Dinuclear/trinuclear iron enzyme
KW - Metalloenzyme
KW - Metallophore
KW - Natural product biosynthesis
KW - RiPPs
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U2 - 10.1016/j.cbpa.2024.102467
DO - 10.1016/j.cbpa.2024.102467
M3 - Review article
C2 - 38772214
AN - SCOPUS:85193444925
SN - 1367-5931
VL - 80
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
M1 - 102467
ER -