Biosynthesis of Isoprenoids

Isoprenoids (= terpenoids or terpenes) are constructed from isoprene (2-methyl-butadiene) units  

They are assigned to the groups given in Table 37 according to the number of building blocks. 

1 Hemiterpenes Isoprene, 3,3-dimethylallyl alcohol, isopentenol, isoamyl alcohol 

2 Monoterpenes Constituents of essential oils, e.g., geraniol, menthol, and thymol, and of iridoids, e.g., loganin and secologanin 

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Spurgeon SL, Porter JW (1981) In biosynthesis of isoprenoid compounds. In Porter JW, Spurgeon SL (eds) John Wiley and Sons, New York, p 1... 

Rohdich, F., Wungsintaweekul, J., Fellermeier, M. et al. (1999) Cytidine 5 -triphosphate-dependent biosynthesis of isoprenoids YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocy-tidyl-2-C-methylerythritol. Proceedings of the National Academy of Sciences of the United States of America, 96, 11758-11763. 

Klein-Marcuschamera, D., Ajikumara, P.K. and Stephanopoulos, G. (2007) Engineering microbial cell factories for biosynthesis of isoprenoid molecules beyond lycopene. Trends in Biotechnology, 25, 417-424. 

SCHWENDER, J., SEEMANN, M LICHTENTHALER, H.K., ROHMER, M., Biosynthesis of isoprenoids (carotenoids, sterols, prenyl side-chains of chlorophylls and plastoquinone) via a novel pyruvate/glyceraldehyde 3-phosphate non-mevalonate pathway in the green alga Scenedesmus obliquus, Biochem. J., 1996, 316, 73-80. 

Eisenreich W, Bacher A, Arigoni D et al (2004) Biosynthesis of isoprenoids via the non-mevalonate pathway. Cell Mol Life Sci 61 1401-1426... 

Schoenwaelder MEA (2002) Physode distribution and the effect of thallus sunburn in Flormosira banksii (Fucales, Phaeophyceae). Bot Mar 45 262-266 Schoenwaelder MEA, Clayton MN (2000) Physode formation in embryos of Phyllospora comosa and Flormosira banksii (Phaeophyceae). Phycologia 39 1-9 Schwender J, Gemunden C, Lichtenthaler HK (2001) Chlorophyta exclusively use the 1-deoxyxylulose 5-phosphate/2-C-methylerythritol 4-phosphate pathway for the biosynthesis of isoprenoids. Planta 212 416 123... 

A detailed mechanistic study of acid-catalysed monocyclization of 5,6-unsaturated epoxides, such as (66), has now provided compelling evidence for a pathway in which the oxirane C—O cleavage and the C—C bond formation are concerted. These experimental results are now further supported by theoretical evidence for a concerted mechanism of the oxirane cleavage and A-ring formation in epoxysqualene cyclisation, obtained at the RHF/6-31G and B3LYP/6-31 + G levels. The chemical pathway thus parallels the mechanism of the enzymatic cyclization that plays a role in the biosynthesis of isoprenoids. 

Elimination usually involves loss of a proton together with a nucleophilic group such as -OH, -NH3+, phosphate, or pyrophosphate. However, as in Eq. 13-18, step c, electrophilic groups such as -COO-can replace the proton. Another example is the conversion of mevalonic acid-5-pyrophosphate to isopentenyl pyrophosphate (Eq. 13-19) This is a key reaction in the biosynthesis of isoprenoid compounds such as cholesterol and vitamin A (Chapter 22). The phosphate ester formed in step a is a probable intermediate and the reaction probably involves a carbo-cationic intermediate generated by the loss of phosphate prior to the decarboxylation. 

Foster, J.M., Pennock, J.F., Marshall, I. and Rees, H.H. (1 993) Biosynthesis of isoprenoid compounds in Schistosoma mansoni. Molecular and Biochemical Parasitology 61, 275-284. 

Chemler JA, Yan Y, Koffas MA. 2006. Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae. Microb Cell Fact 5 20-28. 

John W. Porter and Sandra L. Spurgeon, "Biosynthesis of Isoprenoid Compounds" Vol.l. A Wiley-Interscience Publication, John Wiley and Sons., New York, (l98l). 

HK Lichtenthaler, J Schwender, A Disch, M Rohmer. Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a mevalonate-independent pathway. FEBS Lett 400 271-274, 1997. 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

Porter, J. W., and Spurgeon, S. L. (1981, 1983) Biosynthesis of Isoprenoid Compounds, Vols. 1 and 2. John Wiley Sons, New York. 

One of the more exciting and recent advances in the field of plant biochemistry has been the discovery of the mevalonate-independent pathway for the biosynthesis of isoprenoids (Fig. 10.4). This new pathway, referred to a the methyl-erythritol-phosphate or MEP pathway for the first intermediate committed solely to the biosynthesis of isoprenoids, was first discovered in prokaryotes capable of accumulating hopenes, the equivalent of eukaryotic sterols. 6,17 The MEP pathway has since been confirmed in plants and, not surprisingly, has been localized to chloroplasts.18 Operation of the MEP pathway is intimately related to the reactions of CO2 fixation and photosynthesis, as evidenced by the two immediate precursors pyruvate and phosphoglyceraldehyde for this pathway. Two important features of this pathway are that mevalonate is not an intermediate in the plastidic synthesis of isopentenyl (IPP) and dimethylallyl diphosphate, (DMAPP), and this pathway... 

Be and for the biosynthesis of isoprenoids via the nonmeval-onate pathway. Condensation of 43 with 3-amino-l-hydroxy-acetone phosphate (47) (biosynthesized from D-erythrose 4-phosphate) affords pyridoxine 5 -phosphate (48, Fig. 5A). A sequence of elimination, tautomerization, and water addition precedes cyclization via an aldol condensation (26, 27). Then, pyridoxine 5 -phosphate can be converted into pyridoxal 5 -phosphate (39) by oxidation with molecular oxygen. 

Figure 11 Biosynthesis of isoprenoid type cofactors. 18, Heme a 39, pyridoxal 5 -phosphate 43, 1-deoxy-D-xylulose 5-phosphate 46, thiamine pyrophosphate 83, acetyl-CoA 84, (S)-3-hydroxy-3-methylglutaryl-CoA 85, mevalonate 86, isopentenyl diphosphate (IPP) 87, dimethylallyl diphosphate (DMAPP) 88, pyruvate 89, D-glyceraldehyde 3-phosphate 90, 2C-methyl-D-erythritol 4-phosphate 91, 2C-methyl-erythritol 2,4-cyclodiphosphate 92, 1-hydroxy-2-methyl-2-( )-butenyl 4-diphosphate 93, polyprenyl diphosphate 94, cholecalciferol 95, fS-carotene 96, retinol 97, ubiquinone 98, menaquinone 99, a-tocopherol.

Qureshi N, Porter JW. Conversion of acetyl-coenzyme A to isopentenyl pyrophosphate. In Biosynthesis of isoprenoid Compounds. J. W. Porter and S. L. Spurgeon, eds. 1981. John Wiley, New York. pp. 47-94. 

Gabrielsen M, Rohdich F, Eisenreich W, Grawert T, Hecht S, Bacher A, Hunter WW. Biosynthesis of isoprenoids. A bifunctional IspDF enzyme from Campylobacter jejuni. Eur. J. Biochenr 2004 271 3028-3025. 

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