Natural products and metabolites

Stafford, A. (1991) Natural products and metabolites from plants and plant tissue cultures. In Plant Cells and Culture, (eds Stafford, A. and Warren, G.). The Open University, Milton Keynes, pp. 124-162. 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

The absolute stereochemistries for both compounds were determined by CD analysis of the p-bromobenzoate derivatives. Two other eicosanoids were also isolated from whole animals [198], The trihydroxylated oxylipin 8jR,11S,12R-trihydroxyeicosa-5Z,9 ,14Z,17Z-tetraenoic acid (trioxilin A4,150) was detected in, or isolated from, five starfish species P. miniata, Dermasterias imbricata, Pycnopodia helianthoides, Culcita novaeguinea, and Nardoa tubercolata. Its structure was determined by H and 13C NMR and FAB-MS analyses of the natural product and of an acetonide derivative. The co6 analog of this compound (151) was isolated only from P. helianthoides. The relative stereochemistry in these metabolites (150, 151) was established from a comparison of NMR shifts with malyngic acid, a trihydroxylated C18 compound isolated from Lyngbya majuscula, while the absolute stereochemistry was proposed on the basis of the earlier isolation of 8R-HETE from P. miniata. 

Croteau R, Kutchan TM and Lewis NG. 2000. Natural products (Secondary metabolites). In Buchanan BB, Gruissem W, Jones RL, editors. Biochemistry and Molecular Biology of Plants. Somerset, NJ John Wiley Sons, pp. 1250-1318. 

As in the other -omics, analyses may be directed at a specific metabolite, at all metabolites in a given system in a shot-gun approach, or at accessible groups of molecules in profiling experiments. In that also the technology varies. In addition, the chemistry of different metabolites is very heterogeneous since it involves hydrophobic lipids, hydrophilic carbohydrates, ionic inorganic species, and other secondary natural products and already the choice of solvent in metabolite extraction dictates which types of molecules will be present (Fig. 10.8). Therefore, total metabolome profiling is not possible, because no analytical method will be able to accommodate all the different molecule classes at once. 

Furan-containing molecules are found in both natural products and pharmaceuticals. At one time, furfural was produced in great quantities from corncobs. Perillene, a secondary plant metabolite, is an example of naturally occurring furans. Furan is frequently used as a bioisostere of a benzene ring in medicinal chemistry. For example, Ranitidine (Zantac) marketed by Glaxo was one of the first blockbuster drugs with annual sales over 1 billion dollars. 

Croteau RB et al (2000) Natural products (secondary metabolites). In Buchanan, B, Gruissem, W, Jones, R (eds) Biochemistry and molecular biology of plants. American Society of Plant Physiologists, Rockville, MD, pp. 1250-1268... 

Metabolism. Plant allelochemlcs Ingested by herbivores may be metabolically altered in the digestive tract or after absorption across the gut into the hemolymph. In some cases metabolism of these compounds results in compounds known to be considerably less toxic than the original natural products and thus constitutes true detoxication. On the other hand, the toxicological significance of many of these metabolites is unknown for either their producers or for potential predators. While these allelochemical derivatives may be much more amenable to sequestration than their parent compounds, it will not prove surprising if they are sometimes true detoxication products. 

Marsh G, Stenutz R, Bergman A (2003) Synthesis of Hydroxylated and Methoxylated Polybrominated Diphenyl Ethers - Natural Products and Potential Polybrominated Diphenyl Ether Metabolites. Eur J Org Chem 2566... 

Fig. 1 The integration of systems biology tools with metabolic engineering for advancing industrial biotechnology is herein referred to as industrial systems biology. Industrial systems biology offers the opportunity to introduce new concepts in metabolic engineering and advances the development of cell factories through traditional fermentation for production of natural products and, after the advent of recombinant DNA technology, for the production of recombinant metabolites [1]...

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