%0 Journal Article
%A Amariei, Diana A.
%A Pozhydaieva, Nadiia
%A David, Benoit
%A Schneider, Pascal
%A Classen, Thomas
%A Gohlke, Holger
%A Weiergräber, Oliver H.
%A Pietruszka, Jörg
%T Enzymatic C3-Methylation of Indoles Using Methyltransferase PsmD─Crystal Structure, Catalytic Mechanism, and Preparative Applications
%J ACS catalysis
%V 12
%N 22
%@ 2155-5435
%C Washington, DC
%I ACS
%M FZJ-2022-04465
%P 14130 - 14139
%D 2022
%X Enantioselective methylation is a challenging task in organic chemistry, yet often desirable in drug discovery and optimization. S-Adenosyl methionine (SAM)-dependent methyltransferases (MTases) offer a selective alternative to chemical synthesis and an abundance of potential scaffolds. The crystal structure of C3-indole MTase PsmD from Streptomyces griseofuscus, involved in the biosynthesis of the acetylcholinesterase inhibitor physostigmine, was determined via X-ray crystallography. The amino acid residues essential for catalysis were identified by site-directed mutagenesis, and a mechanism of action was proposed. Furthermore, a PsmD ortholog was identified and characterized. The variant catalyzed enantioselective C-methylation over a broad substrate scope while displaying increased stability. Using this enzyme, preparative-scale enzymatic methylation was performed in cell-free extracts in combination with an SAM recycling system, eliminating the need for cofactor supplementation.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000881780200001
%R 10.1021/acscatal.2c04240
%U https://juser.fz-juelich.de/record/911150