期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 3, 页码 1524-1527出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202013871
关键词
bioalkylation; halide methyltransferase; methylation; protein engineering; SAM analog
资金
- China Scholarship Council [201606150073]
- European Union [722610]
- Projekt DEAL
- Alexander von Humboldt-Stiftung
Biocatalytic alkylations play a crucial role in obtaining chemo-, regio- and stereoselectively alkylated compounds. Recent research has shown that a halide methyltransferase from Chloracidobacterium thermophilum can synthesize SAM, leading to the development of a method for directed evolution of an HMT from Arabidopsis thaliana and identification of a variant that can produce various SAM analogs.
Biocatalytic alkylations are important reactions to obtain chemo-, regio- and stereoselectively alkylated compounds. This can be achieved using S-adenosyl-l-methionine (SAM)-dependent methyltransferases and SAM analogs. It was recently shown that a halide methyltransferase (HMT) from Chloracidobacterium thermophilum can synthesize SAM from SAH and methyl iodide. We developed an iodide-based assay for the directed evolution of an HMT from Arabidopsis thaliana and used it to identify a V140T variant that can also accept ethyl-, propyl-, and allyl iodide to produce the corresponding SAM analogs (90, 50, and 70 % conversion of 15 mg SAH). The V140T AtHMT was used in one-pot cascades with O-methyltransferases (IeOMT or COMT) to achieve the regioselective ethylation of luteolin and allylation of 3,4-dihydroxybenzaldehyde. While a cascade for the propylation of 3,4-dihydroxybenzaldehyde gave low conversion, the propyl-SAH intermediate could be confirmed by NMR spectroscopy.
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