Scopolamine is the active ingredient of motion-sicknessmedicines and eye-exam pupil dilators.

Hyoscyamine, scopolamine's commercial poor relation, findsmore limited pharmaceutical use in smooth-muscle relaxantsand sedatives.

Both drugs are alkaloids, secondary metabolites derived fromsolanaceous flowering plants and botanical kin to tomatoes andpotatoes.

On a scale of 10, scopolamine has a market value of 10;hyoscyamine of 1. Which is why a trio of agricultural chemistsat Kyoto University in Japan introduced into Atropa belladonna(deadly nightshade) a gene that encodes the enzyme thatconverts hyoscyamine to scopolamine. As they report in today'sProceedings of the National Academy of Sciences (PNAS), "Inthe primary transformant and its selfed progeny that inheritedthe transgene, the alkaloid contents of the leaf and stem werealmost exclusively scopolamine."

To contruct the gene, they took the enzyme, hyoscyamine beta-hydroxylase from another plant, Hyoscyamus niger (henbane),and inserted its structural gene sequence, controlled by acauliflower mosaic virus promoter, into the belladonna plantvia an Agrobacterium tumefaciens transformation system.

The Japanese scientists chose A. belladonna as the transgenichost for their metabolic-engineering experiment because it is "atypical hyoscyamine-rich plant." But they suggested that manyother medicinal plants with high hyoscyamine content, but lowon scopolamine, may now become promising candidates for thevalue-added drug.

Before that can happen, cautions Takahashi Hashimoto, leadauthor of the PNAS paper, "further tests in the greenhouse andin the field are necessary to assess the long-term performanceof these transgenic scopolamine-type belladonnas, especiallywith regard to the total yields of alkaloids."

Hashimoto observed that "secondary metabolism is aparticularly attractive target for improving the yields ofdesirable products without markedly affecting basic cellularfunctions."

"This to my mind is a good example of the successfulmanipulation of a medicinal plant to produce a moremarketable product," Peter J. Hylands, vice president and chiefscientist at Escagenetics Corp. of San Carlos, Calif., said of theJapanese feat. "If this technology could be applied to a plantthat produced a medicinal compound extremely difficult tosynthesize, such as taxol, then it would be worthwhile puttingthat transgenic plant into cell culture," he told BioWorld.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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