Biosynthesis of Monoterpene Indole Alkaloids in vitro

The medicinal value of monoterpene indole alkaloids continues to attract interest in their phytochemistry, chemical structure, biosynthesis, and chemothera-peutic activity. Structural complexity and non-profitability of total synthesis, perceived or real shortages in the supply of botanicals, and recent concerns for the environmental impact of wild cropping, made production of these alkaloids in vitro, i.e. by plant cells cultured in bioreactors, a viable prospect. The synthesis and accumulation of monoterpene indole alkaloids in cell cultures received great attention when commercial production of compounds like quinine (1), aj-malicine (2) and catharanthine (6), vinblastine (8) and vincristine (9) appeared attainable. Technologies aimed at increasing alkaloid accumulation by employment of production media, by precursor feeding, elicitation, semi-continuous culture, and by application of enhanced bioreactors were designed to achieve this goal. At present, however, efforts to further promote cell cultures as medici-nals have softened somewhat due to regulatory barriers, but also due to biological barriers. Vinblastine and vincristine, the most desirable Catharanthus alkaloids, did not occur in concentrations which would warrant commercial exploitation of an in vitro process. Research will be required to overcome these barriers. Research into the biosynthesis of monoterpene indole alkaloids, when supplemented with molecular biological approaches, appears to be the most sensitive approach.