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222 Chapter 9
9.6 N-Pyruvoyl-dependent amino acid decarboxylases
A small number of amino acid decarboxylases have been found which show no
requirement for PLP. Historically, the Wrst of these enzymes to be discovered
was histidine decarboxylase from Lactobacillus. The enzyme can, however, be
inactivated by treatment with either sodium borohydride or phenylhydrazine,
suggesting the presence of an electrophilic carbonyl cofactor. This cofactor has
been shown to be an N-terminal pyruvoyl group, which forms an imine linkage
with the a-amino group of l-histidine. The amide carbonyl group then acts as
an electron sink for decarboxylation, as shown in Figure 9.16.
Other examples of N-pyruvoyl-dependent decarboxylases include an
S-adenosyl methionine decarboxylase and an aspartate decarboxylase from
E. coli.
9.7 Imines and enamines in alkaloid biosynthesis
Certain a-amino acids are used as biosynthetic precursors for the assembly of
alkaloid natural products. Examples of alkaloid natural products include nicotine,
morphine and strychnine, shown in Figure 9.17.
The complex carbocyclic skeletons of these alkaloid natural products are
assembled by intricate biosynthetic pathways. Many of the carbon–carbon
bond-forming steps involve imines and enamines derived from a-amino acids.
For example, lupinine is a quinolizidine alkaloid found in Lupinus plants which
is assembled from two molecules of l-lysine as shown in Figure 9.18. The amino
acid is Wrst decarboxylated by a PLP-dependent decarboxylase enzyme to give a
N
N
H
H
− CO 2
NH 2
O
O
NHEnz
N
N
H
H
O − O
NH +
NHEnz
O
N
N
H
AEnz
H
H
NH +
NHEnz
O −
N
+
NH 3
N
H
H
N
H
O
NHEnz
N
H
NH +
NHEnz
Figure 9.16 Mechanism for N-pyruvoyl-dependent histidine decarboxylase.
O
O