Isoprenoid pathways carotenoid synthesis

FIGURE 5.3.1 Parts of the isoprenoid pathways to carotenoids. 1 = MEP pathway. 2 = GGPP synthesis. 3 = Carotenoid biosynthetic pathway. 4 = Carotenoid degradative pathways. Enzyme abbreviations and enzyme activities are defined in Table 5.3.1. 

Figure 9.2. The inherent metabolic flexibility of the isoprenoid pathway leading to the synthesis of some carotenoid pigments. Genes coding for two enzymes capable of acting on carotenoid structures were introduced into Escherichia coli which had already been transformed to give it the capacity to make p,p-carotene. Both of the two introduced new enzymes (one shown with red arrows and the other with blue arrows) acted on multiple substrates because of their lack of specificity. The resulting matrix of transformations means that nine different products can be made by just two tailoring enzymes. (Adapted from Umeno et al. ° who used data from Misawa et al. °)...

Carotenoids of higher plants, algae, and fungi are C40 tetraterpenes biosynthesized by the well-known isoprenoid pathway [1, 5, 6, 8, 17, 18]. The early steps, involving the formation of the C5 isoprenoid units and the subsequent synthesis of prenyldiphosphate intermediates, are common to all classes of terpenoids. 

The IPP monomer serves as the universal building block for the production of all isoprenoids, including artemisinine, carotenoids, and Taxol. Thus, an engineered strain with high potential for generating IPP provides a platform for production of a variety of complex isoprenoids. The presence of two IPP synthesis pathways allows two approaches for engineering such strains. One is to introduce a heterozygous pathway and the other is to alter or modify the native pathway. Both approaches have been accomplished in E. coli. 

Thorough biochemical analysis of carotenoid biosynthesis, classical genetics, and more recently molecular genetics resulted in the elucidation of the main routes for the synthesis of acyclic and cyclic carotenoids at a molecular level (Sandmann 2001). Little is known, however, about the biosynthesis of carotenoids containing additional modifications of the end groups, the polyene chain, the methyl groups, or molecular rearrangements that contribute to the tremendous structural diversity of carotenoids. At present, hundreds of individual carotenoids have been characterized (Britton et al. 1998), and novel carotenoids continue to be isolated. All carotenoids are derived from the isoprenoid or terpenoid pathway. 

All carotenoids are derived from the isoprenoid or terpenoid pathway. From prenyl diphosphates of different chain lengths, specific routes branch off into various terpenoid end products. The prenyl diphosphates are formed by different prenyl transferases after isomerization of IPP to DMAPP by successive T-4 condensations with IPP molecules. Condensation of one molecule of dimethylallyl diphosphate (DMADP) and three molecules of isopentyl diphosphate (IDP) produces the diter-pene geranylgeranyl diphosphate (GGDP) that forms one-half of all C40 carotenoids. The head-to-head condensation of two GGDP molecules results in the first colorless carotenoid, phytoene. Phytoene synthesis is the first committed step in C40 carotenoid biosynthesis (Britton et al. 1998, Sandmann 2001). 

The analysis of tomato color mutants found in Solanum lycopersicum or in crosses with related wild species, as well as genetic engineering studies have clarified enormously the bios3uithetic pathway of carotenoids. Carotenoids, as other plastid isoprenoids, derive from isopentenyl diphosphate (IPP). IPP used in the synthesis of these compounds may arise at some developmental stages partly from the mevalonic (MVA) pathway [23], but it is mainly synthesized through the methyler-ythritol-4-phosphate (MEP) pathway [24]. The first enzyme of this pathway. 

IPP, a Cs-compound, is the source of carotenoids, isoprenoids, terpenes, quinones, and phytol of BChls and Chls. There are two known independent pathways of IPP synthesis the classical mevalonate (MVA) pathway and the alternative, non-mevalonate, l-deoxy-D-xylulose-5-phosphate (DOXP) pathway [19, 20]. In the MVA pathway, acetyl-coenzyme A is converted to IPP through mevalonate. The enzymes and genes involved in this pathway are well studied [21]. The DOXP pathway was found in the 1990s, and in this pathway, pyruvate and glyceraldehyde are converted to IPP. 

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