title: Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?
abstract: 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.
authors.affiliation: Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain. bordes@uji.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Bordes
authors.affiliation: Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain. al189587@alumail.uji.es.
authors.forename: José
authors.initials: J
authors.lastname: Recatalá
authors.affiliation: Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain. swiderek@uji.es.|Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz 90-924, Poland. swiderek@uji.es.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Świderek
authors.affiliation: Departament de Química Física i Analítica, Universitat Jaume I, Castellón 12071, Spain. moliner@uji.es.
authors.forename: Vicent
authors.initials: V
authors.lastname: Moliner
mesh_terms: D002384:Catalysis; D020134:Catalytic Domain; D004851:Epoxide Hydrolases / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry*; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010088:Oxidoreductases / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D005656:Fungal Proteins; D010088:Oxidoreductases; C023111:epoxidase; D008049:Lipase; C431349:lipase B, Candida antarctica; D004851:Epoxide Hydrolases
keywords: CALB; Candida antarctica lipase B; catalysis; enzyme promiscuity; epoxide hydrolase; quantum cluster models; reaction mechanism; sEH; trans-diphenylpropene oxide