4.1. Terpene indole alkaloids biosynthesis
The chief precursor in the synthesis of expensive anticancer drugs
vinblastine and vincristine are strictosidine. This compound undergoes a
series of reactions and forms compounds of diverse structure and
biological function. Strictosidine is formed from the combination of
tryptamine and secologanin, which are synthesized through the indole and
mevalonate pathway, respectively. Firstly, in the TIA synthesis pathway,
geraniol is formed from geranyl diphosphate (GDP) in the presence of
geraniol synthase (GES). Later, geraniol is hydroxylated to
10-hydroxy-geraniol catalyzed by geraniol 10-hydroxylase, which has a
regulatory role in the TIAs synthesis pathway. Following a series of
steps, loganin is formed. In the last stage of the iridoid pathway, in
the presence of secologanin synthase, loganin is converted into
secologanin. On the other hand, a single enzymatic reaction comprises of
conversion of L-tryptophan catalyzed by tryptophan decarboxylase yields
tryptamine. Condensation of secologanin and tryptamine lead to the
formation of strictosidine, a central intermediate of the TIAs pathway,
by an enzyme strictosidine synthase. In the vindoline pathway, this
compound undergoes a series of enzymatic reactions to produce
catharanthine and vindoline, which includes two recently discovered
enzymes dihydroprecondylocarpine synthase (PAS) and dehydrogenase
dihydroprecondylocarpine synthase (DPAS)
(Caputi et al., 2018) that converts an
immediate stemmadenine acetate to tabsersonine and catharanthine. This
reaction is catalyzed by vacuolar class III peroxidase to produce α3’,
4”anhydrovinblastine, which after several steps, converted into
vinblastine and vincristine (Dutta et al.,
2005; Zhou et al., 2010;
Zhu et al., 2014) (Fig. 8 ).