Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?

Molecules

Isabel Bordes¹  José Recatalá¹  Katarzyna Świderek¹  Vicent Moliner¹  Diego A. Alonso² 

[1] Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain; E-Mails:Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain;

关键词: Candida antarctica lipase B;    CALB;    epoxide hydrolase;    sEH;    reaction mechanism;    trans-diphenylpropene oxide;    enzyme promiscuity;    catalysis;    quantum cluster models;   

DOI  :  10.3390/molecules201017789

来源: mdpi

【 摘 要 】

Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrolase (sEH) formed by a nucleophile-histidine-acid catalytic triad and an oxyanion hole typical for molecular structures derived from processes of α/β hydrolases. In this work we are exploring these similarities and proposing a Ser105Asp variant of CALB as a new catalyst for epoxide hydrolysis. In particular, the hydrolysis of the trans-diphenylpropene oxide (t-DPPO) is studied by means of quantum cluster models mimicking the active site of both enzymes. Our results, based on semi-empirical and DFT calculations, suggest that mutant Ser105Asp CALB is a good protein scaffold to be used for the bio-synthesis of chiral compounds.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.