Seeking shikimic

A major component of the bird flu drug, it is in short supply

one way to prepare for the bird flu epidemic is to store large quantities of the drug Tamiflu. The drug blocks the enzyme responsible for helping the virus break the host cell membrane to get out, and so 'traps' it, preventing its spread to healthy cells.

Tamiflu is synthesized from shikimic acid which is found in many plants and micro-organisms as a precursor to aromatic amino acids.

Currently, shikimic acid is extracted from the seeds of star anise (Illicium verum), the fruit of which is used to make a Chinese cooking spice. Compared to other sources, the seeds of star anise have the highest concentration of shikimic acid (3-7 per cent), but the plant attains flowering age after six years of growth. This is a bottleneck in the production of the drug in large quantities.

Indian scientists assessed the shikimic acid content of local flora in the Western Ghats. They reported in the March 25 issue of Current Science that among the 193 flowering (angiosperms) and 17 naked seed-bearing (gymnosperms) plant species studied, the gymnosperms have a mean shikimic acid content of 1.5 per cent and the angiosperms, 0.17 per cent. The highest amounts of shikimic acid (5 per cent) were obtained from the leaves of Araucaria excelsa, the Norfolk Island pine. The team reported: "Extraction from leaves will be preferred over fruits because the volume of biomass offered by the leaves would make it economically feasible".

Arif Ali, professor of biotechnology at the Jamia Millia Islamia, Delhi, disagreed with the viability of the solution. "Gymnosperms have a slow growth rate. To obtain the desired quantity of shikimic acid from the leaves, many plants need to be sacrificed and we could soon run out of the source," he said. Moreover, Western Ghats is an important hotspot of biodiversity and needs to be protected.

Another alternative is to use micro-organisms, like E coli, to synthesize the chemical. But, large quantities of shikimic acid are toxic to the microbes and limit the amount that can be produced. "Synthesizing shikimic acid with cell-free extracts in bioreactors is a better option. Bioreactors are large chambers where the required compounds are added for artificial synthesis," said Ali.

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