Structural highlights
Publication Abstract from PubMedalpha-Ketoglutarate-dependent mononuclear non-haem iron (alphaKG-NHFe) enzymes are catalytically versatile, yet OkaE is unique for synthesizing azetidine rings via C-C bond formation. Here, we report the unexpected multifunctionality of OkaE, which catalyzes sequential oxidations. Isotopic labelling studies demonstrate that a second O(2) molecule participates in sequential epoxidation and ring cleavage, incorporating two oxygen atoms within a single catalytic cycle to form the previously unknown structure, neuokaramine IV. Crystal structures of the OkaE*Co(II)*alphaKG*okaramine A complex unveil a unique methionine-pi interaction network that facilitates substrate binding. Mutational and crystallographic analyses suggest this network fine-tunes substrate orientation relative to the metallo-centre, activating distinct reaction pathways at the 3a-OH or C8a positions. QM/MM simulations indicate that dynamic rotation of the Fe(IV)=O species initiates the cycle, enabling reaction bifurcation. This study elucidates the structural and mechanistic basis of OkaE's reactivity, highlighting its potential as a programmable biocatalyst for natural product diversification. Structural and mechanistic insights into azetidine-associated alphaKG-NHFe enzyme OkaE with multifunctional catalysis.,Wang X, Yu J, Liu T, Zhang X, Ju M, Xie Z, Naowarojna N, Ping L, Dong Y, Gong B, Xie Y, Nie Y, Hsiang T, Wu R, Zhang L, Liu P, Zhu G, Yan W, Liu X Nat Commun. 2026 Feb 17. doi: 10.1038/s41467-026-69519-5. PMID:41702921[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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