Nicotinamide coenzyme biomimetics for biocatalysis

Abstract

With the term "enzyme" we define a natural protein able to catalyse a chemical reaction. Whilst this term was coined only in 1878,[1] after using fermentation techniques for millennia, the first scientific observation of enzymatic activity dates back to the previous century and refers to the meat breaking capability of gastric fluids.[2] By now scientists have established that enzymes are necessary to sustain life, ranging from microorganisms to complex animals, and are invaluably resourceful from a biotechnology point of view.Enzymes, appointed as Nature's catalysts (biocatalysts), accelerate the rate of chemical reactions, reducing the activation energy required for the chemical transformation by stabilising the transition state of the reaction or by destabilising the reagents' ground state energy. Different mechanisms of enzyme catalysis are now recognised, with the most common ones being catalysis by complexation, acid/base catalysis, covalent catalysis, catalysis by desolvation and electrostatic catalysis. [3] Table 1. Definitions of selectivities shown by enzymes. Definition ChemoselectivityActing on a single type of functional group, while leaving the others unchanged RegioselectivityActing only on one functional group situated on a specific position on the substrate, leaving other identical functional groups unchanged StereoselectivityActing only on one enantiomer of a racemic substrate mixture; converting a prochiral substrate into one enantiomer or diastereomerNo matter the mechanism, the key to enzymes' activity lays in their three-dimensional structure. Their linear series ofL L-amino acids (primary structure), driven by intramolecular hydrophobic, hydrophilic, ionic and covalent interactions, folds spontaneously in a distinctive secondary and tertiary structure, and can eventually oligomerise to a quaternary structure. Within this structure, different domains can be recognised, which assist in functions such as enzyme stability or interactions with (in)organic molecules (cofactors) or other proteins. The catalytic domain of an enzyme, the active site, has evolved to catalyse a specific physiologically relevant transformation of a compound, the substrate. The mode in which an enzyme binds its substrate was initially thought to be according to the famous