Fig. 3: Hydroxylation of evodiamine by plant P450s.
From: Orthologue inference-based enzyme mining for diversification of the anti-cancer evodiamine scaffold
a Enzymatic reaction scheme shows the conversion of evodiamine into two main hydroxylated products. Structures of compounds 7 and 8 were elucidated by NMR spectroscopy. Bold bonds indicate COSY correlations, and single-headed arrows denote HMBCs. b Extracted ion chromatograms from in vivo feeding assays show substrate (m/z 304) and hydroxylated products (m/z 320). Molecular docking of evodiamine into AlphaFold2-predicted structures of Tel3451 using AutoDock Vina revealed binding conformations consistent with the formation of c compound 7 and d compound 8. The protein surface is shown within 5 Å of the docked substrate and clipped to enhance visualization. Evodiamine, the heme cofactor, phenylalanine residues involved in substrate binding, and the conserved cysteine liganded to the heme iron are shown as ball-and-stick models. Carbon atoms of evodiamine positioned near the heme iron are labeled.
