Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Angew Chem Int Ed Engl. 2017 Mar 27;56(14):4033-4036. doi: 10.1002/anie.201609375. Epub 2017 Mar 1.
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.
S-腺苷甲硫氨酸依赖性甲基转移酶（MTs）在天然产物的生物合成和表观遗传过程中起着决定性的作用。MTs 催化杂原子甚至碳原子的甲基化，而在许多情况下，这在常规合成中是一个具有挑战性的反应。然而，C-MTs 通常具有高度的底物特异性。在这里，我们表明来自灰色链霉菌的 SgvM 具有扩展的底物范围，无论是亲核试剂还是亲电试剂。除了其生理底物 4-甲基-2-氧代戊酸外，SgvM 还可以催化β-碳原子上的丙酮酸、2-氧代丁酸、2-氧代戊酸和苯丙酮酸的（二）甲基化。手性相高效液相色谱分析表明，2-氧代戊酸的甲基化具有 R 选择性，而 2-氧代丁酸与 S-腺苷乙硫氨酸的乙基化反应生成 S-对映体 3-甲基-2-氧代戊酸。因此，SgvM 可以成为不对称生物催化 C-烷基化反应的有价值的工具。
