Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

7 Enzymatic Carbon–Carbon
Bond Formation
7.1 Introduction
The formation of carbon–carbon bonds is central to biosynthesis, which is the
assembly of carbon-based compounds within living cells. Most of these compounds
are primary metabolites – molecules such as amino acids, carbohydrates
and nucleic acids which are necessary to support life. Many organisms also
produce secondary metabolites – molecules whose presence is not essential for
the survival of the cell, but which often have other biological properties such as
defence against micro-organisms or communication with other organisms. In
this chapter we shall analyse the types of enzymatic reactions used in the
assembly of the carbon skeletons of primary and secondary metabolites, and
also carbon–carbon cleavage reactions involved in their degradation.
A carbon–carbon bond consists of a pair of electrons contained within a
Wlled molecular orbital. Formation of a carbon–carbon bond can be achieved
either by donation of a pair of electrons from one carbon atom to an empty
orbital on another carbon atom, or by the combination of two single electron
species. Examples of these processes are illustrated in Figure 7.1, involving:
(1) nucleophilic attack of a carbanion onto an electron-accepting carbonyl
group;
(2) electrophilic attack of a carbocation onto an electron-rich alkene;
(3) recombination of two phenoxy radicals.
We shall meet examples of each of these types of carbon–carbon formation
reactions in this chapter.
One general point to note is that carbanions and carbocations are highenergy
species which can usually only be generated under strenuous reaction
conditions in organic chemistry. How then are they generated by enzymes that
work at neutral pH with relatively weak acidic and basic groups The answer is
that carbanion and carbocation intermediates in enzyme-catalysed reactions
must be highly stabilised, either by neighbouring groups in the substrate molecule,
or by the enzyme active site, using the type of enzyme–substrate interactions
mentioned in Section 2.7. This stabilisation will be explained where
possible in the following examples; however, in some cases the means by which
high-energy intermediates are stabilised is not fully understood.
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