Rationalization of Bioacylation of High‐Value Aroma Chemicals and Their Interactions With Olfactory Receptors via Homology Modelling

ABSTRACT

The present work describes an eco‐compatible biotechnological process for quantitatively producing seven fragrance esters through the enzymatic acylation of the corresponding aromatic/benzylic alcohols. The impact of the modulation of some parameters, such as the amount and lipase nature, the acyl donor and the reaction time, on the efficiency of the enzymatic acylation of benzyl alcohol as the study model was checked. For the first time, two cheap and commercially available free lipases, Candida rugosa lipase and Porcine pancreatic lipases, have been used to acylate aromatic/benzylic alcohols using anhydride acids as irreversible acyl donors at neat. The optimal conditions were applied for the bioacylation of phenol, phenylmethanol, 2‐phenylethanol, and 1‐phenylethanol. The obtained results show an important impact of both nucleophile ( 1–4 ) and acyl donor (acetic anhydride or isobutyric anhydride) on the bioacylation and that in function of the used lipase. Conversion rates ranged from 48.5% to 100%. DFT calculations at B3LYP 6–311G (d, p) basis set were adopted for geometry optimization, stability and reactivity studies of all targeted compounds, including HOMO/LUMO, Δ E _GAP , dipole moment, electronegativity and electrophilicity. With an energy gap of 6.2352 eV, compounds 4 , 1a , and 3b are more active than compounds 1 , 2a , and 3b (8.2235 eV). Ramachandran plots are used to examine the structural properties and stability of proteins. Furthermore, the interactions between olfactory receptors (OR1D2, OR8G1, OR1A1, OR2W1, and OR2J3) and all of the targeted compounds were investigated using molecular docking via homology modelling. These compounds' average binding energies on the five receptors varied from −4.7 to −7.5 kcal/mol. This process was mainly driven by hydrophobic interaction. The results of the molecular docking investigation suggest that OR1D2 is the best receptor for benzylic compounds. Furthermore, compared to the acetate derivatives and the parent alcohol, the isobutyrate derivatives exhibit stronger interactions with all of the investigated ORs. To validate the more stable complexes (Ligand‐OR1D2), molecular dynamic simulations were performed. The best results were recorded with complexes: 1a‐OR1D2, 2a‐OR1D2, 2b‐OR1D2 and 4b‐OR1D2.