Trends in Plant Science
Volume 5, Issue 7, 1 July 2000, Pages 271-272
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Molecular ‘pharming’ with plant P450s

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Isoflavone synthase

Many plant secondary metabolites are derived from the phenylpropanoid pathway, including lignin, tannins, anthocyanins and many phytoalexins. Isoflavones are produced via a branch of the phenylpropanoid pathway. Taxonomically they are limited primarily to legumes, in which the first committed step in biosynthesis is catalyzed by a P450, isoflavone synthase (IFS)7. IFS converts the flavanone substrates liquiritigenin and naringenin to the isoflavones daidzein and genistein, respectively (Fig. 1

IFS metabolic engineering

Armed with the gene for IFS, researchers could now demonstrate the potential for engineering isoflavone production in plants normally lacking IFS (Ref. 1). Arabidopsis does not have IFS and does not make isoflavones, but it does produce the IFS substrate naringenin, which is normally involved in the production of kaempferol and quercetin glycosides, as well as anthocyanins and condensed tannins11. Arabidopsis plants transformed with the soybean IFS gene driven by a strong constitutive promoter

Isoflavones as phytoestrogens

Evidence that isoflavones could act as phytoestrogens was available in the 1940s when sheep grazing on clover with high levels of formononetin was linked to sheep infertility. The compound causing the problem was traced to daidzein, which is produced from formononetin in the sheep rumen12. Isoflavonoids generating the most widespread medical interest today include daidzein, genistein and coumestrol, as well as isoflavone metabolites such as equol (Fig. 1). It is thought that the proposed

Phytoestrogens and hormone-related disorders

The observed effects of phytoestrogen consumption in animals demonstrate the potential efficacy of these compounds, and have generated interest in the use of phytoestrogens for the treatment and prevention of hormone-related disorders in humans15. The potential of phytoestrogens is supported by a correlation between east Asian societies where soy is a primary foodstuff, and reduced incidence of heart disease, osteoporosis, breast cancer, prostate cancer and menopausal symptoms in comparison

Phytoestrogens and infants

Many breast-milk substitutes containing soy have significant levels of daidzein and genistein, such that the daily intake of isoflavones in 4-month-old infants fed on substitutes based on soy protein would be approximately ten times that which has estrogenic effects in adults. Moreover, the combined concentrations of genistein and daidzein in plasma from 4-month-old infants fed soy formula were more than 10 000 times greater than typical infant plasma estradiol concentrations18. Although these

Phytoestrogen ‘nutraceuticals’

Our increasing awareness that compounds found in food can function in capacities well beyond simple nutrition has bolstered the idea that various foods might have an impact on conditions previously thought to be unrelated to diet. This has resulted in an explosion in the number of phytoestrogen dietary supplements being marketed to consumers. If the information currently available is representative of the actual potential for dietary treatment of hormone-related conditions by phytoestrogens,

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