Table 2. Selection of Well-Characterized Biocatalytic Transformations with Potential for Synthesis.
| reaction and enzyme family | comments and references |
|---|---|
| Ester and Amide Formation and Hydrolysis | |
| hydrolases | good substrate range and excellent stereoselectivity74,98−105 |
| carboxylic acid reductasesa | fatty acids and aromatic carboxylic acids; require ATP148−150 |
| Reduction of Ketones and Aldehydes to Alcohols | |
| alcohol dehydrogenases | good substrate range; stereocomplementary enzymes available; require NADH or NADPH; equilibrium107−112 |
| Reduction of Carboxylic Acids to Aldehydes | |
| carboxylic acid reductases | fatty acids and aromatic carboxylic acids; require NADPH and ATP149,150 |
| Reduction of CC Double and Triple Bonds | |
| ene-reductases | substrate requires an electron-withdrawing group (carbonyl, nitrile, or nitro); require NADH or NADPH151−153 |
| Reductive Amination of Ketones and Aldehydes | |
| imine reductases and reductive aminases | stereocomplementary enzymes available; require NADPH; equilibrium114,143,144 |
| transaminases | stereocomplementary enzymes available; require amine as amino-donor; equilibrium113,141 |
| amino acid dehydrogenases and amine dehydrogenases | require NADH or NADPH; equilibrium114,143,144 |
| Oxidation of Alcohols to Ketones/Aldehydes (and Carboxylic Acids) | |
| alcohol dehydrogenases | good substrate range; stereocomplementary enzymes available; require NAD+ or NADP+; equilibrium107−112 |
| oxidases | require O2 and form H2O2 as byproduct124 |
| Hydroxylation of C–H Bonds | |
| P450 monooxygenases | require O2 and NADPH; upscaling might be challenging; vast variety of enzymes available120,124,154−158 |
| flavin-dependent monooxygenases | phenolic substrates; require O2 and NADPH159 |
| dioxygenases | dihydroxylation of aromatics; require O2160 |
| (unspecific) peroxygenases | broad substrate scope, require H2O2; good scalability; moderate regioselectivity161,162 |
| C–O Bond Formation and Cleavage | |
| cobalamin-dependent methyltransferases | aromatic methyl ether formation and cleavage; equilibrium; require anaerobic conditions163 |
| SAM-dependent methyltransferases | aromatic and aliphatic ether formation; require SAM cofactor; troublesome upscaling164 |
| Baeyer–Villiger Oxidation | |
| Baeyer–Villiger monooxgenases | require O2 and NADPH |
| C–C Bond Formation | |
| aldolases | broad variety of enzymes known; equilibrium165 |
| (de)carboxylases | carboxylation of aromatic molecules or styrenes; require bicarbonate, equilibrium118,166 |
| hydroxynitrile lyases | stereocomplementary enzymes available; require HCN; spontaneous background reaction; equilibrium167,168 |
| SAM-dependent methyltransferases | require SAM cofactor; troublesome upscaling164 |
| acyl transferases | Friedel–Crafts acylation of resorcinols; require esters as acyldonors116,165 |
| CC Bond Cleavage: Decarboxylation | |
| (de)carboxylases | aromatic carboxylic acids or cinnamic acids as substrates, equilibrium118,166 |
| P450 monooxygenases | (functionalized) fatty acids to terminal alkenes120,162 |
| Halogenation | |
| flavin-dependent halogenases | aromatic substrates (tryptophan derivatives); require O2 and NADH169 |
a
Carboxylic acid reductases can also be used for amide or ester formation by letting the thioester intermediate react with an amine or alcohol instead of a hydride [NAD(P)H] as the nucleophile.