8FTR

SgvM methyltransferase with MTA and alpha-ketoleucine

8FTR の概要

• エントリーDOI: 10.2210/pdb8ftr/pdb
• 分子名称: Methyltransferase, 5'-DEOXY-5'-METHYLTHIOADENOSINE, ZINC ION, ... (5 entities in total)
• 機能のキーワード: methyltransferase, biosynthetic protein
• 由来する生物種: Streptomyces griseoviridis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37404.36

構造登録者

Kuzelka, K.,Nair, S.K. (登録日: 2023-01-13, 公開日: 2023-11-01)

主引用文献

Ju, S.,Kuzelka, K.P.,Guo, R.,Krohn-Hansen, B.,Wu, J.,Nair, S.K.,Yang, Y.
A biocatalytic platform for asymmetric alkylation of alpha-keto acids by mining and engineering of methyltransferases.
Nat Commun, 14:5704-5704, 2023

PubMed Abstract: Catalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvM as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvM and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.

PubMed: 37709735
DOI: 10.1038/s41467-023-40980-w

実験手法

X-RAY DIFFRACTION (2.13 Å)