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100 1 _ |a Amariei, Diana A.
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245 _ _ |a Enzymatic C3-Methylation of Indoles Using Methyltransferase PsmD─Crystal Structure, Catalytic Mechanism, and Preparative Applications
260 _ _ |a Washington, DC
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520 _ _ |a 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.
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700 1 _ |a Pozhydaieva, Nadiia
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700 1 _ |a David, Benoit
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700 1 _ |a Schneider, Pascal
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700 1 _ |a Classen, Thomas
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700 1 _ |a Gohlke, Holger
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700 1 _ |a Weiergräber, Oliver H.
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700 1 _ |a Pietruszka, Jörg
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773 _ _ |a 10.1021/acscatal.2c04240
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