Asymmetric C‐Alkylation by the S‐Adenosylmethionine‐Dependent Methyltransferase SgvM. Issue 14 (1st March 2017)

• Record Type: Journal Article
• Authors: Sommer‐Kamann, Christina; Fries, Alexander; Mordhorst, Silja; Andexer, Jennifer N.; Müller, Michael
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 14(2017)
• Page Start: 4033
• Page End: 4036
• Publication Date: 2017-03-01
• Subjects: asymmetric methylation -- biocatalysis -- enzyme catalysis -- ethylation -- isotopes; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201609375
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Enzymatic alkylation : The methyltransferase SgvM from Streptomyces griseoviridis has a broad substrate scope with respect to both the nucleophilic and electrophilic reaction partner. It can thus catalyze the asymmetric methylation and ethylation of a variety of α‐oxo acids.