Structure-Guided Engineering of D-Fructose-6-Phosphate Aldolase for Improved Acceptor Tolerance in Biocatalytic Aldol Additions

被引：19
作者：
Soler, Anna [1 ]
Gutierrez, Mariana L. [1 ]
Bujons, Jordi [1 ]
Parella, Teodor [2 ]
Minguillon, Cristina [3 ]
Joglar, Jesus [1 ]
Clapes, Pere [1 ]
机构：
[1] CSIC, IQAC, Dept Biol Chem & Mol Modeling, ES-08034 Barcelona, Spain
[2] Univ Autonoma Barcelona, Dept Chem, Serv Ressonancia Magnet Nucl, Bellaterra, Spain
[3] Univ Barcelona, Fac Farm, Dept Farmacol & Quim Terapeut, E-08007 Barcelona, Spain
来源：
ADVANCED SYNTHESIS & CATALYSIS | 2015年 / 357卷 / 08期
关键词：
aldol reaction; aldolases; enzyme catalysis; D-fructose-6-phosphate aldolase; iminocyclitols; lyases; mutagenesis; D-FRUCTOSE; 6-PHOSPHATE; FRUCTOSE-6-PHOSPHATE ALDOLASE; ESCHERICHIA-COLI; POLYHYDROXYLATED PYRROLIZIDINES; CHEMOENZYMATIC SYNTHESIS; INHIBITORY PROPERTIES; ORGANIC-SYNTHESIS; DIHYDROXYACETONE; DERIVATIVES; IMINOCYCLITOLS;
D O I：
10.1002/adsc.201500073
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
A structure-guided redesign of D-fructose6-phosphate aldolase from Escherichia coli (FSA) was devised for improving the acceptor tolerance towards a-substituted and conformationally constrained aldehydes. FSA A129S/R134X/A165G/S166G and L107Y/A129G/R134X/A165G/S166G variants, where X was R, V, P, or S, were the most suited biocatalysts for dihydroxyacetone, hydroxyacetone and glycolaldehyde additions to 20 a-substituted N-Cbz-aminoaldehydes (Cbz=benzyloxycarbonyl) including pyrrolidine and piperidine derivatives. Full kinetic stereocontrol for si-si face addition of the aldolase-bound nucleophile to the N-Cbz-aminoaldehyde carbonyl was observed, furnishing the corresponding D-threo configured aldol adduct in >95:5 dr as assessed by NMR. After reductive amination, 47 different iminocyclitols were identified and characterized. In some examples partial racemization of the corresponding aldehyde was observed, which appears to be produced mostly during the aldol addition reactions.
引用
收藏
页码：1787 / 1807
页数：21
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