title: Asymmetric C-Alkylation by the S-Adenosylmethionine-Dependent Methyltransferase SgvM.
abstract: S-Adenosylmethionine-dependent methyltransferases (MTs) play a decisive role in the biosynthesis of natural products and in epigenetic processes. MTs catalyze the methylation of heteroatoms and even of carbon atoms, which, in many cases, is a challenging reaction in conventional synthesis. However, C-MTs are often highly substrate-specific. Herein, we show that SgvM from Streptomyces griseoviridis features an extended substrate scope with respect to the nucleophile as well as the electrophile. Aside from its physiological substrate 4-methyl-2-oxovalerate, SgvM catalyzes the (di)methylation of pyruvate, 2-oxobutyrate, 2-oxovalerate, and phenylpyruvate at the β-carbon atom. Chiral-phase HPLC analysis revealed that the methylation of 2-oxovalerate occurs with R selectivity while the ethylation of 2-oxobutyrate with S-adenosylethionine results in the S enantiomer of 3-methyl-2-oxovalerate. Thus SgvM could be a valuable tool for asymmetric biocatalytic C-alkylation reactions.
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Christina
authors.identifier: 0000-0001-7406-0880
authors.initials: C
authors.lastname: Sommer-Kamann
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fries
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Silja
authors.identifier: 0000-0001-7274-7451
authors.initials: S
authors.lastname: Mordhorst
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Jennifer N
authors.identifier: 0000-0001-8238-5749
authors.initials: JN
authors.lastname: Andexer
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Michael
authors.identifier: 0000-0002-2742-4992
authors.initials: M
authors.lastname: Müller
keywords: asymmetric methylation; biocatalysis; enzyme catalysis; ethylation; isotopes