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The concept of metabolic pathway manipulation for the purpose of endowing microorganisms with desirable properties is very old indeed. Metabolic engineering emerged with DNA recombination as the enabling technology. Initially attention was focused, almost exclusively, on the synthetic side of this field: expression of new genes in various host cells, amplification of endogenous enzymes, deletion of genes or modulation of enzymatic activity, transcriptional or enzymatic deregulation, etc. As such, metabolic engineering was, to a significant extent, the technological manifestation of applied molecular biology, with very little engineering content [1]. Stephanopoulos et al. [1] defined metabolic engineering as the directed improvement of product formation or cellular properties through the modification of specific biochemical reaction(s) or the introduction of new one(s) with the use of recombinant DNA technology.

Metabolic engineering in plants involves the modification of endogenous pathways to increase flux toward particular desirable molecules. Giving an example, Ye et al. [2] produced transgenic plants overexpressing the phytoene synthase gene PSY, the daffodil lycopene P-cyclase gene LVY-B, and the Erwinia phytoene desaturase gene crtI to produce a high level of P-carotene accumulation in transgenic rice seeds. "Golden rice" is another good example of the use of metabolic engineering to improve the content of plant vitamin A, which has been hailed as a significant advance in plant nutrient quality.

Vitamin E is important for human and animal health and only synthesized in higher plants and other oxygenic photosynthetic organisms [3-5]. For human and animal health, a-tocopherol has the highest vitamin E activity [6], partly because it is retained in the human body in preference to other tocopherols and tocotrienols [7]. The function of vitamin E in mammals is to act as a free-radical scavenger for inhibiting lipid oxidation. A high intake of vitamin E is associated with a decreased risk of certain cancers and neurodegenerative and cardiovascular diseases [8]. Furthermore, new functions of vitamin E as an antihypercholesterolemic and immunos-timulatory agent have been proposed [9].

However, species and types of plant tissues vary greatly in their total tocochro-manol content and composition. Oilseeds are the richest source of vitamin E, with total tocochromanol levels ranging from 330 to 2000 |g per gram of oil [12]. The major form of vitamin E in oilseeds is y-tocopherol. Unfortunately, the vitamin E activity of y-tocopherol is only one tenth that for a-tocopherol. However, in green leaves of higher plants, the total tocochromanol content is very low, but the proportion of a-tocopherol is high [10].

Table 18.1 Important milestones in vitamin E history





Existence of vitamin E recognized by Evans and Bishop when it became clear that this fat-soluble factor (named factor X)


prevented fetal death in animals fed a diet containing rancid lard


Fernholz elucidates structure of vitamin E



Synthesis of vitamin E by Karrer



Revelation by Gordon and colleagues that mature infants had low levels of blood tocopherol and abnormal hemolysis of


erythrocytes, incubated in presence of H202


Study by Bunyan and colleagues on antioxidant impact of vitamin E on polyunsaturated fatty acids



Evidence presented by Boscoboinik that smooth muscle cell proliferation is inhibited by a-tocopherol through protein kinase C




Hydroxyphenylpyruvate dioxygenase is cloned from carrot by Garcia et al.



Discovery by Fechner et al. that the expression of a-tocopherol transfer protein in the liver is induced by a- and P-tocopherol



Norris et al. isolate the gene encoding p-hydroxyphenylpyruvate dioxygenase from Arabidopsis



Shintani D and DellaPenna D clone y-TMT from Arabidopsis thaliana and Synechocystis PCC6803 by genomics-based




Evidence presented by Aratri et al. that increased transcription level of a-tropomyosin is caused by a-tocopherol



Discovery of a-tocopherol as a transcriptional regulator of gene expression via association with a transcription factor


tocopherol-associated protein


Membrane-bound homogentisate phytyltransferase (HPTs) identified from Synechocystis sp. PCC6803 and Arabidopsis by Eva


Collakova and Dean DellaPenna


Peter Dormann et al. identify tocopherol cyclase essential for all tocopherol biosynthesis from Arabidopsis



Dean DellaPenna and colleagues isolate and characterized the


2-methyl-6-phytyl-l,4-benzoquinone/2-methyl-6-solanyl-l,4-benzoquinone methyltransferase (MPBQ/MSBQ MT) from



Alpha-tocopherol modulates two major signal transduction pathways centered on protein kinase C and phosphatidylinositol




DellaPenna et al. prove that vitamin E is essential for seed longevity and for preventing lipid peroxidation during germination



Genetic engineering is used to elevate the tocopherol content in leaves and seeds



Hiroshi Maeda and Dean DellaPenna reveal that tocopherols are required for proper adaptation of phloem loading at low




It is discovered that vitamin E modulates signal transduction in plants by influencing jasmonic acid levels


There is a need to increase vitamin E production through plant engineering in order to meet the demand for human consumption. Numerous studies have been carried out in this field leading to many successful examples of increased vitamin E production. Elevated tocopherol intake has also been reported to reduce the occurrence and severity of several diseases, including heart disease, some cancers, neurodegenerative diseases, and cataracts [11].

The Recommended Daily Allowance (RDA) for vitamin E was originally set at 8 and 10 mg tocopherol for adult women and men, respectively. The new RDA has been raised to 15 to 30 mg for men and women [12]. These amounts can be obtained by eating a wide variety of foods rich in vitamin E. However, daily intake of vitamin E in excess of the RDA (100 to 1000 international units) prevents cardiovascular disease and some cancers, improves immune function, and slows the progression of a number of degenerative human conditions [9]. Because of these health benefits, there is a considerable interest in increasing vitamin E content and altering its composition in favor of a-tocopherol by metabolic engineering in plants [12-15, 18].

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