|
he use of enzymes in organic synthesis has
produced some spectacular successes. For example, Rhodococcus
bacteria can transform acrylonitrile to acrylamide in yields
over 99% with no risk of polymerization or over-oxidation to
acrylic acid. This is used commercially at a scale of 30,000
tons per year. Proteases have found wide usage in laundry detergents.
Enzymes have the advantage that they are enantioselective, easy
to separate from the product, are highly specific, and not least,
are less likely to frighten consumers who have been conditioned
by the media to fear synthetic chemicals. However, because of the
specificity of enzymes, and the real and imaginary limitations of
enzymes, most organic chemists use enzymes only as a last resort.
Many chemists are also unfamiliar with the vast number of enzymes
that are available, their reactions and cofactor requirements, and
the potential side-reactions and problems that can occur with
enzymes. These two books aim to introduce enzymes to organic
chemists with the hope of changing this situation.
Both books are written in textbook style. Each book has its own strengths and weaknesses. For example, Enzymes is definitely not a beautifully-typeset book. On the other hand, the printing in Biotransformations, while nicer, is light and difficult to read. More importantly, both books omit major classes of reactions that could potentially be of immense value to chemists. Here is my biased, incomplete, and subjective summary of some of the reactions that I could find in each book:
| Reaction | Biotransformations | Enzymes |
| Synthesis of amides | √ | √ (not in index) |
| Formation of hydroperoxides by oxygenases | √ | in passing |
| Reactions of sterols / steroids | √ | in passing |
| Cholesterol synthesis from squalene | no | √ |
| Transaminases | in passing | √ |
| Transglutaminases | no | no |
| Halogenation | √ | no |
| Hydrolysis of nitriles | √ | √ |
| Synthesis of epoxides | √ | √ (not in index) |
| Hydrolysis of epoxides | √ | brief mention |
| Enantioselective reduction of ketones | √ | √ |
| Phosphorylation of alcohols by kinases | √ | √ |
| Microbial Baeyer-Villiger reactions | √ | √ |
| Aldol condensation (formation of C-C bonds) | √ | √ |
| Number of references in chapter on hydrolysis | 684 | 361 |
From this table, Biotransformations would appear to have a strong edge in most categories. Part of the difference lies in the much better index in Biotransformations. For example, in Enzymes, addition of O2 to lipids to form hydroperoxides is only indexed under "lipoxygenase" and not under "double bonds", "oxygen", or "hydroperoxides", while all of these are listed in Biotransformations. Biotransformations is also more complete, with better coverage and more references in most chapters. However, Enzymes seems to be better at covering the difficulties and drawbacks of the reactions. Enzymes also has more Larock-style tables showing examples of reactions. For my purposes, which was to learn how to use enzymes to form unusual amide bonds in a peptide, both books, as the kids say, totally sucked.
Enzymes are particularly good at catalyzing hydrolytic reactions. Unfortunately, as with any catalyst, the reaction runs in both directions, and the ratio of substrate to product is determined by their relative thermodynamic stability. Thus, the idea of using a protease in reverse to synthesize peptides as both books suggest, is not likely to win many converts. Nevertheless, for the growing class of pharmaceutical biomolecules, enzyme-catalyzed reactions are a useful tool that organic chemists should become more familiar with.
