期刊
CHEMBIOCHEM
卷 16, 期 7, 页码 1041-1045出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201500074
关键词
amine transaminases; cascade synthesis; enantiopreference; enzyme catalysis; protein engineering
资金
- European Union [KBBE-2011-5, 289350]
- DFG [Bo1862/6-1]
Amine transaminases (ATAs) are powerful enzymes for the stereospecific production of chiral amines. However, the synthesis of amines incorporating more than one stereocenter is still a challenge. We developed a cascade synthesis to access optically active 3-alkyl-substituted chiral amines by combining two asymmetric synthesis steps catalyzed by an enoate reductase and ATAs. The ATA wild type from Vibrio fluvialis showed only modest enantioselectivity (14% de) in the amination of (S)-3-methylcyclohexanone, the product of the enoate-reductase-catalyzed reaction step. However, by protein engineering we created two variants with substantially improved diastereoselectivities: variant Leu56Val exhibited a higher R selectivity (66% de) whereas the Leu56Ile substitution caused a switch in enantiopreference to furnish the S-configured diastereomer (70% de). Addition of 30% DMSO further improved the selectivity and facilitated the synthesis of (1R,3S)-1-amino-3-methylcyclohexane with 89% de at 87% conversion.
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