Molecular Modeling of the Enantioselectivity in Lipase-Catalyzed Transesterification Reactions

Abstract

Two strategies based on the use of subsets for calculating the enantioselectivity in lipase-catalyzed transesterifications using the CHARMM force field were investigated. Molecular dynamics was used in our search for low energy conformations. Molecular mechanics was used for refining these low energy conformations. A tetrahedral intermediate with a rigid central part was used for mimicking the transition state. The energy differences between the transition states of the diastereomeric enzyme-substrate complexes were calculated. The way of defining the subsets was based on two fundamentally different strategies. The first strategy used predefined parts of the enzyme and the substrate as subsets. The second approach formed energy-based subsets, varying in size with the substrates studied. The selection of residues to be included in these energy-based subsets was based on the energy of the interaction between the specific residue or water molecule and the transition state. The reaction studied was the kinetic resolution of secondary alcohols in transesterifications using the Candida antarctica lipase B as chiral biocatalyst. The secondary alcohols used in the study were 2-butanol, 3-methyl-2-butanol, and 3,3-dimethyl-2-butanol.

Candida antarctica Lipase B as Catalyst for Cyclic Esters Synthesis, Their Polymerization and Degradation of Aliphatic Polyesters

“…The polymerization of land d,l-lactide gave only oligomers with M n in the range of 0.2-0.5 kg mol −1 . These experiments confirmed clearly the enantioselectivity of the N-435, which was discussed several times in the literature [57][58][59]. In addition, in 2009 Moeller et al [60] studied eROP of d-lactide at 60 °C in the presence of 10, 15 and 25 wt% of N-435 used as a catalyst.…”

Isohexide and Sorbitol-Derived, Enzymatically Synthesized Renewable Polyesters with Enhanced Tg

“…26 Thus, the reaction rate for bicyclic monomers with secondary alcohols is lower compared with linear monomers with primary alcohols, making unmodified isohexides not the favorite diol substrates in a lipase-catalyzed reaction. Besides displaying regio-selectivity for primary over secondary hydroxyl groups, CALB exhibits pronounced enantio-selectivity for the R-configuration toward the Sconfiguration of secondary hydroxyl groups.…”

A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases

“…[10,15,19,20,34] The results for secondary alcohols are in accordance with complementary methods which model enantioselectivity in hydrolasecatalyzed reactions by evaluating the free energy of enzyme-substrate complexes. [21,35] Small changes in structure lead to small changes in enantioselectivity Intuitively, one would expect that homologous enzymes have identical enantiopreference as it was observed for…”