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@ARTICLE{Amariei:911150,
author = {Amariei, Diana A. and Pozhydaieva, Nadiia and David, Benoit
and Schneider, Pascal and Classen, Thomas and Gohlke, Holger
and Weiergräber, Oliver H. and Pietruszka, Jörg},
title = {{E}nzymatic {C}3-{M}ethylation of {I}ndoles {U}sing
{M}ethyltransferase {P}sm{D}─{C}rystal {S}tructure,
{C}atalytic {M}echanism, and {P}reparative {A}pplications},
journal = {ACS catalysis},
volume = {12},
number = {22},
issn = {2155-5435},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2022-04465},
pages = {14130 - 14139},
year = {2022},
abstract = {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.},
cin = {IBG-4 / IBI-7 / IBOC / IBG-1},
ddc = {540},
cid = {I:(DE-Juel1)IBG-4-20200403 / I:(DE-Juel1)IBI-7-20200312 /
I:(DE-Juel1)IBOC-20090406 / I:(DE-Juel1)IBG-1-20101118},
pnm = {2171 - Biological and environmental resources for
sustainable use (POF4-217) / 5241 - Molecular Information
Processing in Cellular Systems (POF4-524)},
pid = {G:(DE-HGF)POF4-2171 / G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000881780200001},
doi = {10.1021/acscatal.2c04240},
url = {https://juser.fz-juelich.de/record/911150},
}