9KUS

Cryo-EM structure of C-Methyltransferase from Rhododendron dauricum

Summary for 9KUS

• Entry DOI: 10.2210/pdb9kus/pdb
• EMDB information: 62579
• Descriptor: C-Methyltransferase from Rhododendron dauricum (1 entity in total)
• Functional Keywords: methyltransferase, dimer, transferase
• Biological source: Rhododendron dauricum
• Total number of polymer chains: 2
• Total formula weight: 86223.17

Authors

Ye, Y.M.,Dai, Z.D.,Zhang, M.Z. (deposition date: 2024-12-04, release date: 2025-05-21)

Primary citation

Zhang, M.,Bao, Y.O.,Dai, Z.,Qian, Z.,Yu, H.,Zhou, J.J.,Chen, Y.,Wang, Z.,Wang, K.,Cai, M.,Ye, M.
Molecular and Structural Characterization of a Chalcone di- C -Methyltransferase RdCMT from Rhododendron dauricum and Its Application in De Novo Biosynthesis of Farrerol in Pichia pastoris.
J.Am.Chem.Soc., 2025

PubMed Abstract: Methylation plays a crucial role in drug design and optimization. While numerous methyltransferases have been characterized from plants, -methyltransferases, particularly those targeting phenolic skeletons, are rare. In this study, we identified a novel di--methyltransferase RdCMT from the medicinal plant . RdCMT catalyzes a sequential two-step 3'-/5'--methylation of naringenin chalcone, leading to the biosynthesis of farrerol. RdCMT exhibited a strict substrate specificity for chalcones. Through combinatorial catalysis, a series of -methylated flavonoids were synthesized. Moreover, farrerol was synthesized de novo in and with yields of 0.4 mg/g (dry weight) and 149.0 mg/L, respectively. The structure of RdCMT was determined using cryo-electron microscopy (cryo-EM), revealing that residues R328 and G296 significantly influence the substrate specificity of RdCMT. This work not only introduces a potent biocatalyst for the preparation of -methylated flavonoids but also offers insights into the catalytic mechanisms of -methyltransferases.

PubMed: 40331654
DOI: 10.1021/jacs.5c02654

Experimental method

ELECTRON MICROSCOPY (3.42 Å)