9kpu

Crystal structure of FrazP2 in complex with forazoline C

spinqualitylabelsall models 9kpu, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9kpu is a 2 chain structure with sequence from Actinomadura sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: A1EGF, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5J6UCU5_9ACTN Publication Abstract from PubMed Forazoline A, produced by the marine actinomycete Actinomadura sp. WMMB-499, is a unique PK/NRP hybrid macrolactone with promising antifungal in vivo efficacy through a previously unreported mechanism. Although a PKS/NRPS gene cluster was identified as a candidate for forazoline production, the precise biosynthetic pathway and the functions of the tailoring enzymes remain unclear. In this work, the functions of three cytochrome P450 mono-oxygenases (FrazP1P2P3) were characterized. Notably, FrazP2 was found to mediate cyclohexane ring formation from an 1,3,6-triene precursor during forazoline A biosynthesis, as confirmed by genetic and biochemical analysis. To gain structural and mechanistic insight into the activity of FrazP2, the crystal structure of a FrazP2-substrate complex has been solved at 2.3 A resolution. The molecular dynamics simulations and DFT calculations revealed an unprecedented enzyme-catalyzed oxidative cyclization reaction by FrazP2. These findings expand our understanding of the catalytic diversity of cytochrome P450s, contributing to the diversification of natural products and enabling the creation of unnatural derivatives with increased antifungal potency. Cytochrome P450 Mediated Cyclohexane Ring Formation in Forazoline Biosynthesis.,Chen X, Zhang Y, Li S, Liao W, Tao W, Deng Z, Bugni TS, Su H, Zhang F Angew Chem Int Ed Engl. 2025 May 6:e202504925. doi: 10.1002/anie.202504925. PMID:40329414 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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