Synthesis of (1R,3R)-1-amino-3-methylcyclohexane by an enzyme cascade reaction

被引：19

作者：

Skalden, Lilly ^{[1
]}

Peters, Christin ^{[1
]}

Ratz, Lukas ^{[1
]}

Bornscheuer, Uwe T. ^{[1
]}

机构：

[1] Ernst Moritz Arndt Univ Greifswald, Inst Biochem Biotechnol & Enzyme Catalysis, Felix Hausdorff Str 4, D-17487 Greifswald, Germany

来源：

TETRAHEDRON | 2016年 / 72卷 / 46期

关键词：

Amine transaminase; Enoate reductase; Cascade reaction; Protein engineering; Small cyclic substrates; OPTICALLY-ACTIVE AMINES; ASYMMETRIC-SYNTHESIS; CHIRAL AMINES; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; VIBRIO-FLUVIALIS; TRANSAMINASE; AMINOTRANSFERASE; REDUCTASES; RESOLUTION;

D O I：

10.1016/j.tet.2015.11.005

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Amine transaminases (ATAs) are powerful enzymes for the synthesis of chiral amines. Although the request for amines with more than one chiral center is increasing, their synthesis is still challenging. Here we show a casacde reaction combining an enoate reductase (ERED) and an amine transaminase (ATA-VibFlu), which allows access to optically pure (1R,3R)-1-amino-3-methylcyclohexane. Because all known wildtype EREDs show a (S) -selectivity for 3-methylcyclohex-2-enone and the ATA-VibFlu only showed a modest enantioselectivity, different variants of ERED5 and ATAs were investigated and suitable mutant enzymes were identified. In whole cell biocatalyses using the ERED YqjM Cys26Asp/IIe69Thr and the ATA-VibFlu Leu56Ile (1R,3R)-1-amino-3-methylcyclohexane was obtained at high optical purity (97% de). (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：7207 / 7211

页数：5

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