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Introduction and Background Information

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Biotransformations in Organic Chemistry

Abstract

>Any exponents of classical organic chemistry might probably hesitate to consider a biochemical solution for one of their synthetic problems. This would be due to the fact, that biological systems would have to be handled. Where the growth and maintenance of whole microorganisms is concerned, such hesitation is probably justified. In order to save endless frustrations, close collaboration with a microbiologist or a biochemist is highly recommended to set up and use fermentation systems [1, 2]. On the other hand, isolated enzymes (which may be obtained increasingly easily from commercial sources either in a crude or partially purified form) can be handled like any other chemical catalyst.

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Notes

  1. 1.

    The majority of commonly used enzyme preparations are available through chemical suppliers. Nevertheless, for economic reasons, it may be worth contacting an enzyme producer directly, in particular if bulk quantities are required. For a list of enzyme suppliers see the appendix (Chap. 5).

  2. 2.

    After all, the exact structure of a Grignard-reagent is still unknown.

  3. 3.

    Other sectors of biotechnology have been defined as ‘Red’ (biotechnology in medicine), ‘Green’ (biotechnology for agriculture and plant biotech) and ‘Blue’ (marine biotechnology), http://www.EuropaBio.org, http://www.bio.org

  4. 4.

    Only proteases are exceptions to this rule for obvious reasons.

  5. 5.

    For exceptional D-chiral proteins see [61].

  6. 6.

    According to a BBC-report, the sale of rac-thalidomide to third-world countries has been resumed in mid-1996!

  7. 7.

    For a convenient method for controlling the substrate concentration see [85].

  8. 8.

    E. coli has ~4,500 genes and Saccharomyces cerevisiae (baker's yeast) ~6,500 genes.

  9. 9.

    The amino acid sequence of a protein is generally referred to as its ‘primary structure’, whereas the three-dimensional arrangement of the polyamide chain (the ‘backbone’) in space is called the ‘secondary structure’. The ‘tertiary structure’ includes the arrangement of all atoms, i.e., the amino acid side chains are included, whereas the ‘quarternary structure’ describes the aggregation of several protein molecules to form oligomers.

  10. 10.

    Water bound to an enzyme's surface exhibits a (formal) freezing point of about –20°C.

  11. 11.

    PDB entry 3icw, courtesy of U. Wagner.

  12. 12.

    Also called London forces.

  13. 13.

    Also called Coulomb interactions.

  14. 14.

    ‘To use a picture I want to say that enzyme and glucoside must go together like key and lock in order to exert a chemical effect upon each other’, see [94] p. 2992.

  15. 15.

    ‘A precise orientation of catalytic groups is required for enzyme action; the substrate may cause an appreciable change in the three-dimensional relationship of the amino acids at the active site, and the changes in protein structure caused by a substrate will bring the catalytic groups into proper orientation for reaction, whereas a non-substrate will not.’ See [96].

  16. 16.

    Conformational changes are differentiated into hinge- and shear-type movements [98].

  17. 17.

    A ‘record’ of rate acceleration factor of 1014 has been reported. See [100].

  18. 18.

    This phenomenon is denoted as ‘electrostatic catalysis’ and was coined as ‘Circe-effect’ by WP Jencks.

  19. 19.

    By average, enzymes are 100 times bigger than related chemical catalysts.

  20. 20.

    It is important to note that the (modest) pKa of typical amino acid side chains, such as –NH3 + or –CO2– can be substantially altered up to 2–3 pKa-units through neighboring groups within the enzyme environment. As a consequence, the (approximately neutral) imidazole moiety of His can act as strong acid or base, depending on its molecular environment.

  21. 21.

    The following rationale was adapted from [111].

  22. 22.

    The individual reaction rates v A and v B correspond to v A = (k cat/K M)A · [Enz] · [A] and v B = (k cat/K M)B · [Enz] · [B], respectively, according to Michaelis-Menten kinetics. The ratio of the individual reaction rates of enantiomers is an important parameter for the description of the enantioselectivity of a reaction: v A/v B = E (‘Enantiomeric Ratio’, see Sect. 2.1.1).

  23. 23.

    Based on the biotransformation database of Kroutil and Faber (2010) ~14,000 entries.

  24. 24.

    For a discussion of the pitfalls associated with TONs and TOFs see [124].

  25. 25.

    Assuming that each catalyst molecule has a single active site. For enzymes obeying Michaelis-Menten kinetics the TON is equal to 1/k cat.

  26. 26.

    A ‘cofactor’ is tightly bound to an enzyme (e.g., FAD), whereas a ‘coenzyme’ can dissociate into the medium (e.g., NADH). In practice, however, this distinction is not always made in a consequent manner.

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  1. Department of Chemistry Organic & Bioorganic Chemistry, University of Graz, Heinrichstr. 28, A-8010, Graz, Austria

    Prof. Dr. Kurt Faber

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Faber, K. (2011). Introduction and Background Information. In: Biotransformations in Organic Chemistry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17393-6_1

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