Protein self-assembly induces promiscuous nucleophilic biocatalysis in Morita–Baylis–Hillman (MBH) reaction

The chemical industry has seen a remarkable increase in the use of biocatalysis in recent years. Structurally dened spatial distribution of residues in proteins has offered efficient catalysis for a variety of mechanistically unique synthetic transformations. Over a period, the perspective of high specicity in enzyme catalysis has changed and led to the realization that a large population of enzymes is capable of catalyzing multiple reactions. However, non-biological transformations have posed a stiff challenge to biocatalysis. Promiscuous enzymes or protein-based catalysts are key aspirants in this case and have drawn attention from diverse streams of Science. One of the most important synthetic transformations, carbon–carbon bond formation, is realized in natural systems but do not extend to non-biological chemical transformations. For example, MBH reaction has been a notoriously difficult target owing to a sequence of steps that involves mechanism switching based on the substrates and solvents. MBH reaction involves nucleophilic catalysis in a Michael addition rendering enolate that entraps an electrophile to form C–C bond in an aldol condensation and results in a functionally rich molecule. There are no examples of antibodies that can catalyze this reaction. A recent attempt in this direction through directed evolution of engineered enone-binding proteins and another previous attempt met limited success. Protein backbone has several