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[SANET-MG] gm crops for health 3



part 3
gm crops for health?
Minerals
There has been extensive genetic manipulation to improve the mineral nutrition of plants for both macronutrients such as calcium and nitrogen, and micronutrients such as selenium. A 3-fold enhancement of calcium in potato tubers was achieved using an Arabidopsis calcium exchanger and transporter gene. The exchanger had been shortened at the N terminus to eliminate an auto-inhibitory regulatory domain of the protein. Two different promoters were tested, the CaMV promoter and a cell division cycle gene promoter, both of which appeared to have equivalent effects on calcium uptake [58]. The modifications did not affect yield or quality of the potatoes. Milk is currently the main source of calcium in children’s diet, but is that to be soon replaced by fries? Inorganic nitrogen fertilizer is linked to a variety of problems including the pollution of drinking water, harming infants and causing eutrification of water and depletion of oxygen for aquatic animals. Improving utilization of nitrates by crops should lead to human health benefits in terms of cleaner drinking water, which could be offset by increased levels of nitrates in crops. The best way to improve nitrate utilization by crop plants is to phase out chemical fertilizers in favour of organic inputs, which decrease nitrate levels in the water as well as in the crop plants, where cancer-fighting antioxidants, mineral nutrients and micronutrients are also increased [21, 59] (Organic Strawberries Stop Cancer Cells; Organic Farms Make Healthy Plants Make Healthy People). So far, there has been little progress in developing transgenic crops that take up and utilize nitrogen more efficiently [60]. Iron deficiency in food crops plagues much of the globe, particularly Asia. About 40 percent of the world’s women suffer some degree of iron deficiency. Pre-menopausal women are most severely affected by iron deficiency, while men tend to retain iron. Increased dietary iron is desirable and rice is the preferred crop for increasing iron content. Mugineic acid phytosiderophores (siderophores are compounds that bind metals in the soil and enhance their cellular uptake) iron transporters are re-adsorbed by the plant roots. In response to iron deficiency, the phytosiderophores are markedly increased. Transgenic rice modified with barley genes for the precursors of the phytosiderophore produce elevated levels of phytosiderophore and had enhanced tolerance to low iron soil, and had a greater yield than conventional rice on alkaline soil [61, 62]. Constitutive expression of a gene for soybean ferritin in wheat and rice resulted in increased levels of iron in the leaves and stems of transgenic rice but not the grains [63]. The soybean ferritin gene linked to an endosperm specific promoter was expressed in the seeds of maize resulting in elevated iron content [64] (Rice in Asia: Too Little Iron, Too Much Arsenic). Food crops enhanced with elevated iron content must be labelled in the marketplace because iron overload is a significant problem in males, and may lead to haemochromatosis, a disorder of excessive absorption and storage of iron that could damage the liver and other organs, resulting in liver cancer or colorectal cancer. One percent of the population may carry a mutation (hereditary haemochromatosis) that makes them sensitive to iron overload at relatively modest iron intake levels; and there is an association between increasing iron stores and risk of cancer [65]. Selenium is essential for humans, but has a toxic side that makes it poisonous at relatively low levels. In Australia, selenium is generally inadequate for optimum human health, so agronomic bio-fortification of food grains has been proposed [66]. In western USA, on the other hand, high soil selenium levels are encountered. Seleniun toxicity is caused by replacement of protein sulphur with selenium forming selenocysteine, which is needed at low levels but toxic at higher levels. A mouse gene specifying an enzyme selenocysteine lyase was introduced into the Brassica juncea (canola) chloroplast genome to limit accumulation of selenocysteine to mitigate selenium toxicity. The transgenic canola had a reduced content of selenium in its proteins [67]. Like iron and other minerals, selenium is an essential nutrient, but becomes toxic at high levels. It is clear that manipulating single genes to overproduce any mineral (or vitamin) is fraught with difficulties as these essential nutrients are often toxic at inappropriately high levels. This highlights the importance of getting a balanced mineral content in our food, which can only be achieved by moving away from unbalanced external inputs of chemical fertilisers in favour of organic fertilisers [21, 60].

Fatty Acids
Long chain fatty acids are the focus of a great deal of interest because they play an important role in health and nutrition. Long chain polyunsaturated acids are vital for human health. Fish and marine oils are the main sources of long chain polyunsaturated fatty acids, but efforts are being made to modify oil crop plants to produce the essential fish fats. The key fatty acids are eicosapentaenoic acid (20 carbon fatty acid with five unsaturated double bonds) and docosahexaenoic acid (22 carbon fatty acid with six double bonds). Genes from a marine microalga Isochrysis galbana, an oil-producing fungus Mortierella alpina and a green protozoan flagellate Euglena gracillus were used to transform Arabidopsis to modify the plant seed oils to fish fatty acids. The transforming genes were involved in elongating and desaturating the plant fatty acids [68-70]. The crucial long chain polyunsaturated fatty acids were synthesized in Arapidopsis, a tiny plant grown in small petri dishes, which is thus unlikely to produce commercial quantities of the essential fatty acids. The process will have to be transferred to oil crops; but why not grow fish instead? Fish and vegetables together make a much more satisfactory diet, and certainly a more enjoyable meal for most people. Monsanto engineered canola seeds to accumulate stearidonic acid, another long chain polyunsaturated omega-3 fatty acid that has 18 carbons and 4 double bonds. The transgenic canola was modified with genes targeted to the seeds, and included genes for desaturase from the oil fungus Mortierella alpina and from canola [71]. USDA and the University of Nebraska created transgenic soybean to produce stearidonic acid. The soybean was modified with desaturase genes from borage (a tasty salad green) and Arabidopsis, driven by a seed-specific promoter from soybean. Stearidonic acid made up 60 percent of the seed oil in the modified soybean [72]. Sunflower seed oil has been modified with multiple copies of a desaturase gene from castor bean to act on stearic acid, which reduces the quality of sunflower seed oil. The transgenic oil had reduced levels of stearic acid and was superior to unmodified sunflower oil [73]. Antisense technology was used to down regulate a cottonseed desaturase gene resulting in enhanced production of desirable oleic acid and reduced the content of linoelic acid, which is highly undesirable [74]. The modifications of plant fatty acids are impressive, but the impact of the transgenes and transgenic plants on human health remain unknown. As discussed earlier, the protein products of transgenes may have undesirable effects on the immune system. Metabolic engineering in general may create unintended toxins and immunogens. Another factor to take into account is that the essential polyunsaturated fatty acids are also known to be toxic at high levels. There is good evidence that n-3 and n-6 polyunsaturated fatty acids are therapeutic at moderate levels in the diet but they may be detrimental at high levels by causing oxidation stress and forming lipid peroxides which are toxic. Daily intake of the polyunsaturated fatty acids above 10 percent of energy intake is not recommended [75]. Furthermore, high intake of marine fat rich in n-3 polyunsaturated fatty acids may prolong gestation, producing high birth weight [76] and gestational exposure to methylmercury in fish. The n-3 fatty acids interact with the mercury pollutant found in fish and unmask its toxic effects [77].

Amino Acids
Certain amino acids are essential for the human diet because mammals cannot synthesize the amino acids. The essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In addition, the amino acids arginine, cysteine, glycine and tyrosine are considered conditionally essential. Certain crops, such as maize, are not complete foods or feeds because they are deficient in an essential amino acid. Maize is normally deficient in lysine. As indicated earlier, high lysine transgenic maize was approved for commercial release in 2004. The transgenic lysine is modified with a bacterial gene while high lysine maze varieties are already available through conventional breeding. The transgenic maize differs from high lysine maize derived from conventional breeding, which contains storage proteins with elevated lysine. Transgenic maize, on the other hand, has lysine elevated in the metabolic pools, and while it may provide adequate lysine in fodder, the soluble lysine may be lost during processing of the grain [2]. High lysine cereal crops other than maize are considered desirable [79]. Methionine is deficient in some food and feed crops, and there are efforts to enhance methionine levels in these crops. A sunflower seed albumin, rich in the sulphur amino acids methionine and cysteine, was used to modify lupine, a significant feed crop in many countries. The transgenic construct included a herbicide tolerant gene (Bar) and a gus reporter gene. The modified lupine seeds performed significantly better than unmodified lupine in feeding trials [79]. Lupine is not the only legume deficient in sulphur amino acids as all legume storage proteins have low levels of these amino acids, preventing them from being a complete diet. Methionine and cysteine were enhanced in alfalfa by over-expressing an Arabidopsis cystathionine gamma-synthase gene (the first enzyme in the metabolic pathway for methionine). The enzyme was driven by a pea chloroplast rubisco promoter, and directed to the chloroplast by adding a pea rubisco transit sequence. The modified plants were enhanced in both soluble and protein bound methionine and cysteine [80]. Maize has a high methionine-rich storage protein that is usually under-represented in the seeds. A cis-acting regulatory site giving limited messenger RNA stability was replaced by a sequence imparting greater messenger RNA stability, resulting in increased levels of methionine in transgenic seeds. This provided feed and food that did not require addition of synthetic methionine [81]. A bacterial (E. coli) serine acetyl-transferase gene, driven by the CaMV promoter, was transferred to potato to increase cysteine and glutathione. An Arabidopsis transit sequence was added to direct the transgenic protein to the chloroplast. The resulting transgenic potato plants had elevated levels of cysteine and glutathione. Metabolic engineering was used to enhance production of sulphur-containing compounds in potato [82].

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