Directed evolution of aldolases for exploitation in synthetic organic chemistry

被引:60
作者
Bolt, Amanda [1 ,2 ]
Berry, Alan [2 ]
Nelson, Adam [1 ,2 ]
机构
[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England
基金
英国惠康基金; 英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;
关键词
directed evolution; aldolases; substrate specificity; stereochemistry; organic synthesis; carbon-carbon bond formation;
D O I
10.1016/j.abb.2008.01.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This review focuses on the directed evolution of aldolases with synthetically useful properties. Directed evolution has been used to address a number of limitations associated with the use of wild-type aldolases as catalysts in synthetic organic chemistry. The generation of aldolase enzymes with a modified or expanded substrate repertoire is described. Particular emphasis is placed on the directed evolution of aldolases with modified stereochemical properties: such enzymes can be useful catalysts in the stereoselective synthesis of biologically active small molecules. The review also describes some of the fundamental insights into mechanistic enzymology that directed evolution can provide. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:318 / 330
页数:13
相关论文
共 67 条
[1]  
Alexeeva M, 2002, ANGEW CHEM INT EDIT, V41, P3177, DOI 10.1002/1521-3773(20020902)41:17<3177::AID-ANIE3177>3.0.CO
[2]  
2-P
[3]  
[Anonymous], 2004, MODERN ALDOL REACTIO
[4]   Altering protein specificity: techniques and applications [J].
Antikainen, NM ;
Martin, SF .
BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (08) :2701-2716
[5]  
Arnold F.H., 2003, DIRECTED EVOLUTION L
[6]   Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme [J].
Barbosa, JARG ;
Smith, BJ ;
DeGori, R ;
Ooi, HC ;
Marcuccio, SM ;
Campi, EM ;
Jackson, WR ;
Brossmer, R ;
Sommer, M ;
Lawrence, MC .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 303 (03) :405-421
[7]   Directed evolution of an amine oxidase for the preparative deracemisation of cyclic secondary amines [J].
Carr, R ;
Alexeeva, M ;
Dawson, MJ ;
Gotor-Fernández, V ;
Humphrey, CE ;
Turner, NJ .
CHEMBIOCHEM, 2005, 6 (04) :637-639
[8]   In the golden age of organocatalysis [J].
Dalko, PI ;
Moisan, L .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (39) :5138-5175
[9]   Recent advances in aldolase-catalyzed asymmetric synthesis [J].
Dean, Stephen M. ;
Greenberg, William A. ;
Wong, Chi-Huey .
ADVANCED SYNTHESIS & CATALYSIS, 2007, 349 (8-9) :1308-1320
[10]   Structure-based mutagenesis approaches toward expanding the substrate specificity of D-2-deoxyribose-5-phosphate aldolase [J].
DeSantis, G ;
Liu, JJ ;
Clark, DP ;
Heine, A ;
Wilson, IA ;
Wong, CH .
BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (01) :43-52