3.11.2.2. Hydrolases (esterase, lipase): Hydrolytic reactions → Catalyze bond cleavage by the introduction of water; Hydrolysis-formation of esters, amides, lactones, epoxides, nitriles, anhydrides:

Hydrolases:

• hydrolytic cleavage of C-O, C-N, C-C and some other bonds
• favourite class of enzymes for organic chemistry
•  no cofactor needed
• large number of readily available enzymes
• reversible reaction (e.g., amide- or ester-synthesis)
•  relative high stability under non-natural conditions
• often wide substrate range

Lipases:

• Among the biocatalysts in organic synthesis, lipases are the most frequently used. In particular, this class of enzyme is able to perform enantioselective hydrolytic reactions and catalyzes the formation of a wide range of ester and amide bonds.
• natural function - hydrolysis or re-esterification of triglycerides (oils and fats)
• Laundry detergents, modification of natural oils and fats etc.
• offers often excellent stereoselectivity - synthesis of optically pure compounds
• Lipases are highly active in organic solvents
• the most frequently used enzymes in organic synthesis
  • Resolution of alcohols
  • Synthesis of versatile building blocks in organic synthesis
  •  kinetic resolution by hydrolysis
  • kinetic resolution by acylation - activated acyl donors or enol esters (e.g., vinyl or isopropenyl acetate) reaction irreversible as alcohol generated undergo keto-enol tautomerisation

Esterases:

• split esters into an acid and an alcohol
• only few applications for synthesis of optically pure compounds
• moderate enantioselectivity and limited commercial availability

Peptidases, Amidases and Acylases:

• formation and hydrolysis of amide links
• thermodynamically controlled synthesis - shift equilibrium towards synthesis by use of organic solvents, increase concentration of starting material or removing product.
• kinetically controlled synthesis - activation of carboxyl component usually by ester or amide
• Peptide synthesis → coupling of two amino acids
• advantages of enzyme-catalyzed peptide synthesis: mild conditions , high region and enantioselectivity, no racemisation
• large scale production of Aspartame - low-calorie sweetner (DSM, NutraSweet)
• production of Kyotorphin - analgesic dipeptide (Tyr-Arg)
• synthesis of β-lactam peptide antibiotics (penicillines and cephalosporines)

Figure 3.23: Examples of peptidases, amidases and acylases in organic reactions.