Pathways terpenoid biosynthetic

Much attention has been paid to the last step of the formation of monoter-penes and sesquiterpenes, which is catalysed by terpenoid synthases. Over 30 complementary DNAs (cDNAs) encoding plant terpenoid synthases involved in the primary and secondary metabolism have been cloned, characterised, and the proteins heterologously expressed [6]. However, because geranyl diphosphate and farnesyl diphosphate are not readily available substrates, their biotransformation by terpenoid synthases is not economically viable. As a result, considerable effort has been put into engineering the total plant terpenoid biosynthetic pathway in recombinant microorganisms. 

Extracts of Pterogorgia anceps contain a fraction enriched in ancepsenolide metabolites of the polyketide class, one of which (134) is individually deterrent in shipboard assays with T. bifasciatum 0 This last study illustrates that chemical defense mechanisms in gorgonians do not solely rely on the terpenoid biosynthetic pathway. 

Concerning the chemical sjmthesis of this type of compounds, this appears non viable in economic terms and, taking into account that secondary metabolites are often produced in very low amounts in the mother plants, the genetic modification of the terpenoid biosynthetic pathway would be an attractive alternative to obtain a continuous source of these valuable metabolites because it offers the possibility of manipulating cells, tissues or even complete organisms in order to obtain a continuous and accurate source of these secondary metabolites. 

The results from kinetic studies of MVK in Methanococcus jannaschii, showed that the Arg 196 is an essential residue for the function of this enzyme and the Lys 272-Glu 14 plays an important role in maintaining the active site microenvironment that is essential for the catalytic activity of this enzyme [285]. These results suggest that MVK has a regulating role in the terpenoid biosynthetic pathway, as well as in several growth and development processes in plants. 

In D. punctata, JH III is biosynthesized in retrocerebral endocrine organs, the corpora allata (CA) [45]. The sesquiterpenoid skeleton of this compound is formed through the terpenoid biosynthetic pathway from acetyl-CoA. The early steps of this pathway involve the sequential condensation of three acetyl-CoA molecules (3 x 2C) to form the biosynthetic intermediate mevalonate (MVA, 6C). 3-Hydroxy-3-methylglutaryl CoA reductase, which catalyzes the formation of MVA, is thought to be the rate-limiting enzyme in this pathway [59], although the... 

The subcellular compartmentation of terpenoid metabolism is a matter of controversy. Chloroplasts seem to contain the entire terpenoid biosynthetic pathway and appear to be autonomous in regard to terpene biosynthesis. Carotenoids and the side chains of chlorophyll are synthesized in the chloroplasts. Sterols are synthesized in the cytoplasm (Gershenzon and Croteau, 1990). 

K.L.J. (2010) Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control. Proc. Nad. Acad. Sci. US.A., 107, 13654-13659. 

Dewick, P.M. (2001) The mevalonate and deoxyxylulose phosphate pathways terpenoids and steroids. In P.M. Dewick (ed.). Medicinal Natural Products A Biosynthetic Approach, 2nd edn. John WUey Sons Ltd., Chichester, pp. 167-289. 

Ajikumar PK, Xiao W-H, Tyo KEJ, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for taxol precursor overproduction m Escherichia coli. Science 330(6000) 70-74. doi 10.1126/science.l 191652 Albrecht M, Misawa N, Sandmann G (1999) Metabolic engineering of the terpenoid biosynthetic pathway of Escherichia coli for production of the carotenoids p-carotene and zeaxanthin. Biotechnol Lett 21(9) 791-795... 

The production of copious trichome resin products raises the question of whether or not these resins are adaptive. Various proposals have been advanced regarding the defensive role of such compounds and the link between their structural variability and the coevolutionary process. However, there is little evidence linking these compound s biological function to the fine detail of their structural variability. The extent to which the observed chemical variability is an expression of past selection for specific novel chemical deterrents rather than the product of near-random activation of alternative terpenoid biosynthetic pathways is not known. Thus, in looking at the diterpene variability within the Compositae, care should be exercised in automatically associating a discrete adaptive function with each novel chemistry. 

Since GAs as diterpenes share many intermediates in the biosynthetic steps leading to other terpenoids, eg, cytokinins, ABA, sterols, and carotenoids, inhibitors of the mevalonate (MVA) pathway of terpene synthesis also inhibit GA synthesis (57). Biosynthesis of GAs progresses in three stages, ie, formation of / Akaurene from MVA, oxidation of /-kaurene to GA 2" hyde, and further oxidation of the GA22-aldehyde to form the different GAs more than 70 different GAs have been identified. 

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Without proposing an entire biosynthetic pathway, draw the appropriate precursor, either geranyl diphosphate or farnesvl diphosphate, in a conformation that shows a likeness to each of the following terpenoids ... 

Flexibilene, a compound isolated from marine coral, is the only known terpenoid to contain a 15-membered ring. What is the structure of the acyclic biosynthetic precursor of flexibilene Show the mechanistic pathway for the biosynthesis. 

Termination step (radical), 141 Terpenoid. 202-204, 1070-1078 biosynthesis of, 1071-1078 classification of, 1071 DXP biosynthetic pathway of, 1071... 

Terpenoid substances are of broad distribution and diverse function in insects. One set, elaborated by the mandibular glands of Acanthomyops claviger, acts both as a defensive secretion and as an alarm releaser. When fed Cu-labeled acetate or mevalonate, laboratory colonies of these ants produce radioactive citronellal and citral, providing unambiguous evidence for de novo synthesis of these terpenes by the ant. The incorporations of these precursors implicate the mevalonic acid pathway as the likely biosynthetic route. 

Many phytotoxic compounds produced by higher plants are phenolic compounds. Several of these have been implicated in allelopathy. Based on the biosynthetic pathway from which they are derived, phenolic compounds produced by higher plants fall into two general categories 1) terpenoid phenolic compounds derived from five... 

The repertoire of chemicals that can be used for communication is limited by the biosynthetic ability of the insect. Compared to other insect orders, pheromone biosynthesis in Hymenoptera has received little study [191]. However, the biosynthetic origins of chemically diverse hymenopteran semiochemicals likely include aromatic, fatty acid, and terpenoid pathways as well as simple modifications of host-derived precursors. Notable recent studies include the biosynthesis of the fatty acid components (2 )-9-oxodec-2-enoic acid 52 and (2 )-9-hydroxydec-2-enoic acid of the honeybee queen mandibular pheromone from octadecanoic acid [192,193], and the aliphatic alcohol and ester... 

Weathers PJ, Elkholy S, Wobbe KK. (2006) Artemisinin the biosynthetic pathway and its regnlation in Artemisia annua, a terpenoid-rich species. In Vitro Cell Developmental Biol — Plant 42 309-317. 

It is difficult to reconcile the unique chemical structure of tetrodotoxin with that of an animal product. Its structure is not related to that of other animal products by any readily recognized biosynthetic scheme. It is not a terpenoid, not obviously formed from amino acid or carbohydrate units, and apparently not constructed from acetate or propionate units. Nor does it resemble any of the various plant alkaloid patterns. It thus appears to be a very unlikely animal product to result from known biogenetic pathways. In this connection the metabolic incorporation of radioactive precursors using torosa and ]C. granulosa salamanders was studied by Shimizu et al. (47). They observed significant isotopic incorporation into amino acids and steroid metabolites, but they found no such incorporation associated with tetrodotoxin. 

It was only recently that the presence and significance of the sano, or structurally closely related, natural products on land and in the sea has received specific attention (Pietra 1995). Three main conclusions were arrived at (a) the highest fiequency of structural similarities for secondary metabolites occurs with terpenoids fi om anthozoans and land plants (b) biosynthetic routes became adapted to the fimction of the metabolite, such as a defensive one that must persist, or a hormonal one that needs to be rapidly switched off, so, the synthesis of the same compoimd in phylogeneticalfy close organisms should occur by the same pathway, while different biosynthetic routes should be used by phylogenetically distant organisms, and (c) the contribution of marine bacteria to the genes for secondary metabolites in eukaryotes was scarce (Pietra 1995). 

The diverse, widespread and exceedingly numerous class of natural products that are derived from a common biosynthetic pathway based on mevalonate as parent, are synonymously named terpenoids, terpenes or isoprenoids, with the important subgroup of steroids, sometimes singled out as a class in its own right. Monoterpenes, sesquiterpenes, diterpenes and triterpenes are ubiquitous in terrestrial organisms and play an essential role in life, as we know it. Although the study of terrestrial terpenes dates back to the last century, marine terpenes were not discovered until 1955. 

---