Non-mevalonate route

The existence of a similar non-mevalonate route to terpenoids in plants was first reported in 1994. When Duilio Arigoni and co-workers fed different C-labelled forms of glucose to Ginkgo biloba embryos, the G-nuclear magnetic resonance (NMR) spectra of the resulting diterpenes were not what would have been expected from the normal operation of the mevalonate pathway (Cartayrade et al, 1994), but showed an incorporation pattern identical to that seen with the E. coli terpenoids. Subsequent studies employing... 

The non-mevalonate route to terpenoids appears to be localized in the plas-tids. In plant cells, terpenoids are manufactured both in the plastids and the cytosol (Gray, 1987 Kleinig, 1989). As a general rule, the plastids produce monoterpenes, diterpenes, phytol, carotenoids and the side chains of plas-toquinone and a-tocopherol, while the cytosol/ER compartment produces sesquiterpenes, sterols and dolichols. In the studies discussed above, nearly all of the terpenoids labelled by deox30cylulose (Sagner et al, 1998b Eisenreich et al, 2001) and 2-G-methyl erythritol feeding (Duvold et al, 1997) or... 

Scopadulan-type diterpenoids were supposed to be biosymthesized through similar route to that of aphidicolin. However, a non-mevalonate pathway was considered to be involved in this biosynthetic pathway. 

The first specific precursor for terpenoids in the cytoplasma is the Cg molecule mevalonic acid (MVA), which is built via the classical acetate/mevalonate pathway and converted by a series of phosphorylating and decarboxylation reactions into C5 isopentenyldiphosphate (IPP), the universal building block for chain elongation up to C20. In the chloroplasts, the biosynthesis of IPP starts from glyceraldehyde-3-phosphate and pyruvate to give l-deoxy-D-xylulose-5-phosphate (DOXP) via the non-mevalonate pathway as a recently detected alternative IPP route [19]. The reaction is catalyzed by the enzyme DOXP synthase and can be inhibited by a breakdown product of the herbicide clomazone [12]. 

The CDP-derivative 211 of 2-C-methyl-D-erythrito, an intermediate in the non-mevalonate pathway to isoprenoids, has been synthesized from 2-C-methyl-D-erythritol-4-phosphate and CTP, using the transferase which produces 211 naturally. " Enzymatic routes have also been used to produce 211 with multiple specific C-labels, and also 2- C-labelled material. ... 

The German-American biochemist Fritz Albert Lipmann (1899-1986) had discovered Coenzyme A in 1948, while working at the Massachusetts General Hospital in Boston. In 1951, Lynen succeeded at the University of Munich in the isolation of acetyl- Coenzyme A, (acetyl-CoA, the activated form of acetic acid) from yeast cells. Karl Folkers at Merck Sharp Dohme recognised in 1956 mevalonic acid as a critical unit in the terpene biosynthesis, while Lynen documented its formation from three acetyl-CoA moieties and the further route to fatty acids and terpenoids. Recently, another non-mevalonate pathway to terpe-nes (Rohmer pathway) has been discovered, which is not present in humans. 

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