TY  - JOUR
AU  - Amariei, Diana A.
AU  - Pozhydaieva, Nadiia
AU  - David, Benoit
AU  - Schneider, Pascal
AU  - Classen, Thomas
AU  - Gohlke, Holger
AU  - Weiergräber, Oliver H.
AU  - Pietruszka, Jörg
TI  - Enzymatic C3-Methylation of Indoles Using Methyltransferase PsmD─Crystal Structure, Catalytic Mechanism, and Preparative Applications
JO  - ACS catalysis
VL  - 12
IS  - 22
SN  - 2155-5435
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2022-04465
SP  - 14130 - 14139
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000881780200001
DO  - DOI:10.1021/acscatal.2c04240
UR  - https://juser.fz-juelich.de/record/911150
ER  -