Substrate access path-guided engineering of L-threonine aldolase for improving diastereoselectivity. 2022

Wenlong Zheng, and Zhongji Pu, and Lanxin Xiao, and Gang Xu, and Lirong Yang, and Haoran Yu, and Jianping Wu
ZJU-Hangzhou Global Scientific and Technological Innovation Centre, Hangzhou, 311200, Zhejiang, China. yuhaoran@zju.edu.cn.

The L-threonine aldolase from Leishmania major was engineered to improve its diastereoselectivity by a CAST/ISM strategy, providing insights into the relationship between the physico-chemical properties of the substrate access path and diastereoselectivity. The steric hindrance, hydrophobic interaction and π-π interaction cooperated to improve the diastereoselectivity of the enzyme, with a diastereomeric excess (de) value reaching 96.3% from 26.8%.

UI MeSH Term Description Entries
D012696 Glycine Hydroxymethyltransferase A pyridoxal phosphate enzyme that catalyzes the reaction of glycine and 5,10-methylene-tetrahydrofolate to form serine. It also catalyzes the reaction of glycine with acetaldehyde to form L-threonine. EC 2.1.2.1. Serine Aldolase,Serine Hydroxymethylase,Serine Hydroxymethyltransferase,Serine Transhydroxymethylase,Threonine Aldolase,Allothreonine Aldolase,Aldolase, Allothreonine,Aldolase, Serine,Aldolase, Threonine,Hydroxymethylase, Serine,Hydroxymethyltransferase, Glycine,Hydroxymethyltransferase, Serine,Transhydroxymethylase, Serine
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D015202 Protein Engineering Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes. Genetic Engineering of Proteins,Genetic Engineering, Protein,Proteins, Genetic Engineering,Engineering, Protein,Engineering, Protein Genetic,Protein Genetic Engineering
D018320 Leishmania major A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes cutaneous leishmaniasis (LEISHMANIASIS, CUTANEOUS) of the Old World. Transmission is by Phlebotomus sandflies. Leishmania (Leishmania) major,Leishmania tropica major,Leishmania leishmania major,Leishmania leishmania majors,Leishmania majors,Leishmania tropica majors,leishmania major, Leishmania,major, Leishmania leishmania,majors, Leishmania,majors, Leishmania leishmania,majors, Leishmania tropica,tropica major, Leishmania,tropica majors, Leishmania

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