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

共 40 条

[1] Development of an Amine Dehydrogenase for Synthesis of Chiral Amines [J].

Abrahamson, Michael J. ;

Vazquez-Figueroa, Eduardo ;

Woodall, Nicholas B. ;

Moore, Jeffrey C. ;

Bommarius, Andreas S. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (16) :3969-3972

[2] Designer cells for stereocomplementary de novo enzymatic cascade reactions based on laboratory evolution [J].

Agudo, Ruben ;

Reetz, Manfred T. .

CHEMICAL COMMUNICATIONS, 2013, 49 (93) :10914-10916

[3]

Alexeeva M, 2002, ANGEW CHEM INT EDIT, V41, P3177, DOI 10.1002/1521-3773(20020902)41:17<3177::AID-ANIE3177>3.0.CO

[4]

2-P

[5] Optically active amines via lipase-catalyzed methoxyacetylation [J].

Balkenhohl, F ;

Ditrich, K ;

Hauer, B ;

Ladner, W .

JOURNAL FUR PRAKTISCHE CHEMIE-CHEMIKER-ZEITUNG, 1997, 339 (04) :381-384

[6] A Process Concept for High-Purity Production of Amines by Transaminase-Catalyzed Asymmetric Synthesis: Combining Enzyme Cascade and Membrane-Assisted ISPR [J].

Borner, Tim ;

Rehn, Gustav ;

Grey, Carl ;

Adlercreutz, Patrick .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2015, 19 (07) :793-799

[7] Directed Evolution of an Enantioselective Enoate-Reductase: Testing the Utility of Iterative Saturation Mutagenesis [J].

Bougioukou, Despina J. ;

Kille, Sabrina ;

Taglieber, Andreas ;

Reetz, Manfred T. .

ADVANCED SYNTHESIS & CATALYSIS, 2009, 351 (18) :3287-3305

[8] Industrial methods for the production of optically active intermediates [J].

Breuer, M ;

Ditrich, K ;

Habicher, T ;

Hauer, B ;

Kesseler, M ;

Stürmer, R ;

Zelinski, T .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (07) :788-824

[9] Concepts of nature in organic synthesis: Cascade catalysis and multistep conversions in concert [J].

Bruggink, A ;

Schoevaart, R ;

Kieboom, T .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (05) :622-640

[10] Acetate metabolism in a pta mutant of Escherichia coli W3110:: Importance of maintaining acetyl coenzyme a flux for growth and survival [J].

Chang, DE ;

Shin, S ;

Rhee, JS ;

Pan, JG .

JOURNAL OF BACTERIOLOGY, 1999, 181 (21) :6656-6663

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