In Silico Evaluation of Enzymatic Tunnels in the Biotransformation of α-Tocopherol Esters.

Motivation: α-Tocopherol is a molecule obtained primarily from plant sources that are important for the pharmaceutical and cosmetics industry. However, this component has some limitations such as sensitivity to oxygen, presence of light, and high temperatures. For this molecule to become more widely used, it is important to carry out a structural modification so that there is better stability and thus it can carry out its activities. To carry out this structural modification, some modifications are carried out, including the application of biotransformation using enzymes as biocatalysts. Thus, the application of a computational tool that helps in understanding the transport mechanisms of molecules in the tunnels present in the enzymatic structures is of fundamental importance because it promotes a computational screening facilitating bench applications. Objective: The aim of this work was to perform a computational analysis of the biotransformation of α-tocopherol into tocopherol esters, observing the tunnels present in the enzymatic structures as well as the energies which correspond to the transport of molecules. Method: To carry out this work, 9 lipases from different organisms were selected; their structures were analyzed by identifying the tunnels (quantity, conformation, and possibility of transport) and later the calculations of substrate transport for the biotransformation reaction in the identified tunnels were carried out. Additionally, the transport of the product obtained in the reaction through the tunnels was also carried out. Results: In this work, the quantity of existing tunnels in the morphological conformational characteristics in the lipases was verified. Thus, the enzymes with fewer tunnels were RML (3 tunnels), LBC and RNL (4 tunnels), PBLL (5 tunnels), CALB (6 tunnels), HLG (7 tunnels), and LCR and LTL (8 tunnels) and followed by the enzyme LPP with the largest number of tunnels (39 tunnels). However, the enzyme that was most likely to transport substrates in terms of α-tocopherol biotransformation (in relation to the Emax and Ea energies of ligands and products) was CALB, as it obtains conformational and transport characteristics of molecules with a particularity. The most conditions of transport analysis were α-tocopherol tunnel 3 (Emax: -4.6 kcal/mol; Ea: 1.1 kcal/mol), vinyl acetate tunnel 1 (Emax: -2.4 kcal/mol; Ea: 0.1 kcal/mol), and tocopherol acetate tunnel 2 (Emax: -3.7 kcal/mol; Ea: 2 kcal/mol).