Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?

• Published in: Molecules
• Main Authors: Bordes, Isabel, Recatalá, José, Świderek, Katarzyna, Moliner, Vicent
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI 2016
• Subjects: Candida antarctica lipase B; CALB; epoxide hydrolase; sEH; reaction mechanism; trans-diphenylpropene oxide; enzyme promiscuity; catalysis; quantum cluster models; Jaume; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10234/159486; https://doi.org/10.3390/molecules201017789

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. This work was supported by the Spanish Ministerio de Economía y Competitividad for project CTQ2012-36253-C03, Universitat Jaume I (project P1•1B2014-26), Generalitat Valenciana (PROMETEOII/2014/022 and ACOMP/2014/277 projects), the Polish National Center for Science (NCN) (grant 2011/02/A/ ST4/00246, 2012–2017), the Polish Ministry of Science and Higher Education (“Iuventus Plus” program project no. 0478/IP3/2015/73, 2015-2016), and the USA’s National Institutes of Health (ref. NIH R01 GM065368). The authors acknowledge computational resources from the Servei d’Informàtica of Universitat Jaume I and from the Technical University of Lodz.