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[SANET-MG] tomatoes enhanced for folate production using a synthetic human gene



Folic acid deficiency  is a major  factor in neural tube birth defects ,
such defects are very prevalent in modern society. The deficiency  is
also implicated in breast cancer and heart disease. The most simple
procedure has been to add folate to bakery products. The publication
below shows how tomatoes may be enhanced by genetic modification using a
synthetic copy of a human gene. The use of synthetic copies of human
genes in food crops does deserve special attention and study.

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.040
Folate biofortification in tomatoes by engineering the pteridine branch
of folate synthesis

Rocío Díaz de la Garza *, Eoin P. Quinlivan , Sebastian M. J. Klaus *,
Gilles J. C. Basset *, Jesse F. Gregory III , and Andrew D. Hanson *
Departments of *Horticultural Sciences and Food Science and Human
Nutrition, University of Florida, Gainesville, FL 32611

Plants are the main source of folate in human diets, but many fruits,
tubers, and seeds are poor in this vitamin, and folate deficiency is a
worldwide problem. Plants synthesize folate from pteridine,
p-aminobenzoate (PABA), and glutamate moieties. Pteridine synthesis
capacity is known to drop in ripening tomato fruit; therefore, we
countered this decline by fruit-specific overexpression of GTP
cyclohydrolase I, the first enzyme of pteridine synthesis. We used a
synthetic gene based on mammalian GTP cyclohydrolase I, because this
enzyme is predicted to escape feedback control in planta. This
engineering maneuver raised fruit pteridine content by 3- to 140-fold
and fruit folate content by an average of 2-fold among 12 independent
transformants, relative to vector-alone controls. Most of the folate
increase was contributed by 5-methyltetrahydrofolate polyglutamates and
5,10-methenyltetrahydrofolate polyglutamates, which were also major
forms of folate in control fruit. The accumulated pteridines included
neopterin, monapterin, and hydroxymethylpterin; their reduced forms,
which are folate biosynthesis intermediates; and pteridine glycosides
not previously found in plants. Engineered fruit with intermediate
levels of pteridine overproduction attained the highest folate levels.
PABA pools were severely depleted in engineered fruit that were high in
folate, and supplying such fruit with PABA by means of the fruit stalk
increased their folate content by up to 10-fold. These results
demonstrate that engineering a moderate increase in pteridine production
can significantly enhance the folate content in food plants and that
boosting the PABA supply can produce further gains.

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