Biotransformation catalytic mechanism

As an example, it has been estimated that for the industrial production of fine chemicals, biotransformations should accomplish a minimum space-time yield of 0.1 g l-1 h-1 and a minimum final product concentration of 1 g l-1, while for pharmaceuticals, the minimum requirements are 0.001 g l-1 h-1 and 0.1 g l1 for volumetric productivity and product concentration, respectively [6]. Analysis of enzymes with recognized industrial potential, such as cytochrome P450, showed that some of the parameters are already within industrially relevant ranges [7]. The improvements achieved with these biocatalysts through protein, cell, and process engineering are based on the understanding of their molecular arrangement and catalytic mechanisms. 

Hydrolysis of epoxides, esters, amides, and related structures is an important biotransformation reaction that limits the therapeutic activity of many drugs and generates therapeutically active drugs from prodmg structures. In a few cases, hydrolytic reactions can generate a toxic structure. Epoxide hydrolases and esterases are members of the a/(3 hydrolase-fold family of enzymes (Morisseau and Hammock, 2005 Satoh and Hosokawa, 2006). Although their substrate specificities are radically different (e.g., lipids, peptides, epoxides, esters, amides, haloalkanes), their catalytic mechanisms are similar. All of these enzymes have an active site catalytic triad composed of a nucleophilic serine or cysteine residue (esterases/amidases), or aspartate residue (epoxide hydrolases) to activate the substrate, and histidine residue and glutamate or aspartate residues that act cooperatively in an acid—base reaction to activate a water molecule for the hydrolytic step. 

Electronic properties are of particular interest in SMRs because they control the cleavage and formation of covalent bonds characteristic of a biotransformation reaction (i.e., the catalytic step). Correlations between electronic parameters and catalytic parameters obtained from in vitro studies (e.g., or cat) allow a rationalization of substrate selectivity and some insight into reaction mechanism. 

All the data presented so far indicate that catalytic antibodies will certainly help us to gain more insight into enzyme mechanisms rather than playing an important role in preparative biotransformations. 

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