Lipazlar morita-baylis-hillman reaksiyonunu nasil katalize ederler

Enzymes have the ability to catalyze different reactions and this make them outstanding natural catalysts. The use of biocatalysts in industrial applications is an significant strategy, especially the development of an environmentally friendly catalyst that can selectively accelerate the carbon-carbon coupling reactions. Morita Baylis Hillman (MBH) is a widely used carbon-carbon bond formation reaction which converts simple starting materials into products with extensive functional groups. In recent years, the use of the MBH reaction in the synthesis of pharmaceutically important products has led to numerous studies about the development of novel biocatalyst that can catalyze this reaction with high efficiency. Even though the catalytic machinery required for the MBH reaction is present in enzymes, no proteins have naturally evolved to catalyze this industrially important reaction. In the literature, several proteins are known to show promiscuous catalytic activity towards the MBH reaction. However, in order to repurpose these proteins, information on binding site and catalytic elements are essential, that can only be investigated by computational methods. In this study, theoretical active site models (theozymes) including substrates of 2-cyclohexen-1-one and 4-nitrobenzaldehyde were generated and they were matched with the crystal structure of the of Burkholderia cepacia lipase (BCL), one of the proteins that show promiscuous activity against the MBH reaction, to determine the binding sites of substrates within BCL and catalytic elements it uses to catalyze the MBH reaction. As a result, 2 binding sites consist of 9 different catalytic motifs (catalytic triads and catalytic dyads) were identified and accordingly cluster models were generated for Binding Site 1. The energy calculations of triad 1 (ASP264-HIS286-SER87) and triad 2 (GLU289- HIS286-SER87) were calculated by using density functional theory at the B3LYP/6-31G(d) level. The results suggest that triad 2 has the lowest energy pathway and that is more favorable for catalyzing the MBH reaction than BCL's native catalytic triad which is triad 1. The study was also revealed promising proteins that have the ability to catalyze the MBH reaction, have not been previously reported in the literature.