Monoterpenoid indole alkaloids (MIAs) are a large
group of plant-derived natural products with a range
of pharmacological properties. Examples of MIAs are
camptothecin—used to treat cancer—and quinine—the antimalarial
drug of choice till the mid of the last century. Madagascar
periwinkle, Catharanthus roseus, the best-characterized
MIA-producing plant species, is the source of the valuable MIAs
vincristine and vinblastine, which are used directly or as
derivatives for the treatment of several cancer types. Owing to
the extremely low concentrations (0.0002% fresh weight),
production of vincristine and vinblastine is expensive and
availability of the drug is sensitive to environmental and political
instability in the production countries. Therefore, biotechnologybased
production of MIAs in microorganisms or alternative plant
hosts has been proposed as a sustainable substitute; however,
progress has been hampered by the lack of knowledge of the
enzymes responsible for MIA biosynthesis, particularly in the
secologanin pathway (Fig. 1). Secologanin is the monoterpenoid
(also called iridoid or secoiridoid) branch end point and is
coupled to tryptamine by strictosidine synthase (STR) to form
strictosidine, the universal MIA precursor in plants. The
secologanin pathway has broad importance as many plant species
accumulate iridoids and secoiridoids (including secologanin) as
end products without incorporating them into complex alkaloids.
Many (seco)iridoids are bioactive themselves, with among others
anticancer, antimicrobial and anti-inflammatory activities1–4.
Iridoids are also pheromones in some insect species, and as
such can be employed for pest management in agriculture and the
control of insect-related disease vectors5,6.