Isoprenoid biosynthetic pathway products

Fig. 4 Proposed biosynthetic pathways for the production of ipsdienol in I. pini and frontalin in D. spp. Both pathways utilize an isoprenoid biosynthetic pathway to produce geranyl diphosphate...

Evidence for de novo synthesis of pheromone components was obtained by showing that labeled acetate and mevalonate were incorporated into ipsdienol by male Ips pini [103,104]. Similarly, labeled acetate and other labeled intermediates were shown to be incorporated into frontalin in a number of Dendroctonus species [105]. Possible precursors to frontalin include 6-methyl-6-hep-ten-2-one, which was incorporated into frontalin by D. ruffipennis [106]. The precursor 6-methyl-6-hepten-2-one also was shown to be converted to bre-vicomin in the bark beetle, Dendroctonus ponderosae [107]. In addition, the expression patterns of HMG-CoA reductase and HMG-CoA synthase are tightly correlated with frontalin production in Dendroctonus jeffreyi [108, 109]. A geranyl diphosphate synthase cDNA from I. pini was also isolated, functionally expressed, and modeled [110]. These data indicate that the de novo isoprenoid biosynthetic pathway is present in bark beetles. A variety of other monoterpene alcohols such as myrcenol, pityol, and sulcitol are probably synthesized through similar pathways [111]... 

It appears that, in beetles, pheromone production is regulated by JH III, despite the variations in biosynthetic pathways. JH apparently regulates pheromone production in beetles that utilize both fatty acid and isoprenoid biosynthetic pathways [8,98]. Environmental and physiological factors will in turn regulate production of JH. The endocrine regulation of pheromone production in the beetles has been best studied with regard to the bark beetles. 

As presented in Table 1.2, over half of reported marine natural products are derived from the isoprenoid biosynthetic pathway (56%), with the remainder split mainly between amino acid (19%) and acetogenin (20%) pathways. Secondary metabolites falling into the categories of nucleic acids and carbohydrates comprise only 1%. Such low levels are somewhat surprising given the fundamental importance of such classes of compounds as primary metabolites. 

Fig. 12.1. The isoprenoid biosynthetic pathway. Intermediates and products are shown in black and enzymes in blue. Components of the mevalonate-mdependent DOXP pathway are shown in green. The HMGR inhibitors (statins) are shown m red.

Table 6.4 Range of 5-values of natural products from land plants. Values in [] for C4-plants. S H-values of carbohydrates from CAM-plants can be up to -t-50%o. Most S O-values are correlated to those of the water present at the (bio)synthesis of the compounds. The S C- and S H-values of isoprenoids depend on the biosynthetic pathway products from the mevalonate pathway are generally more depleted in and less depleted in as compared to those from...

Of the two existing isoprenoid biosynthetic pathways (Fig. 3), DXP is used by most prokaryotes for production of IPP and dimethylallyl diphosphate (DMAPP) [65,66]. With the available knowledge of the genes involved in the DXP pathway, several groups have studied the impact of changed expression levels of these genes on the production of reporter terpenoids. Farmer and liao reconstructed the isoprene biosynthetic pathway in Escherichia coli (E. colt) to produce lycopene, which was used as an indication... 

Isoprenoid biosynthetic pathways produce an astonishing variety of products in different cell types and different species. Despite this diversity, the beginning of isoprenoid biosynthesis appears to be identical in most of the species investigated (e.g., yeast, mammals, and plants). (HMG-CoA = / -hydroxy-/3-methylglutaryl-CoA)... 

The biosynthesis of sterols takes place via the protracted sterol/isoprenoid biosynthetic pathway (Chapter 1). Although the major portion of the carbon flux through this pathway is normally directed into sterols, several branches exist leading to the production of other isoprenoid compounds needed by the cell, such as ubiquinone, dolichol and isopentenyl adenine. Total carbon flux is regulated through the enzymes of the early, or common, portion of the pathway of which the most important is HMG-CoA reductase. Distribution of carbon between the various end products is regulated at later stages of the pathway. 

The emerging picture is that when sterol biosynthesis is suppressed, gross changes in the carbon flux through the sterol/isoprenoid biosynthetic pathway are mediated by HMG-CoA reductase. This decreases the supply of biosynthetic intermediates available for non-sterol products, which normally are synthesized in far smaller quantity than are sterols. To assure a sufficient supply of these intermediates for needed non-sterols such as dolichol and ubiquinone, later steps in the sterol/isoprenoid biosynthetic pathway are also down-regulated [141]. 

Anthony JR, Anthony LC, Nowroozi F, Kwon G, Newman JD, Keasling JD (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11 13-19... 

Anthony JR, Anthony LC, Nowroozi F, Kwon G, Newman JD, Keasling JD (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11 13-19 Aubel D, Morris R, Lennon B, Rimann M, Kaufmann H, Folcher M, Bailey JE, Thompson CJ, Fussenegger M (2001) Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics. J Antibiot 54 44-55 Baltz RH (2006) Molecular engineering approaches to peptide, polyketide and other antibiotics. Nat Biotechnol 24 1533-1540... 

Isoprenoids are intermediates and products of the biosynthetic pathway that starts with mevalonate and ends with cholesterol and other sterols. 

Abstract Pheromones are utilized by many insects in a complex chemical communication system. This review will look at the biosynthesis of sex and aggregation pheromones in the model insects, moths, flies, cockroaches, and beetles. The biosynthetic pathways involve altered pathways of normal metabolism of fatty acids and isoprenoids. Endocrine regulation of the biosynthetic pathways will also be reviewed for the model insects. A neuropeptide named pheromone biosynthesis activating neuropeptide regulates sex pheromone biosynthesis in moths. Juvenile hormone regulates pheromone production in the beetles and cockroaches, while 20-hydroxyecdysone regulates pheromone production in the flies. 

Poly(3HB) synthesis in various subcellular compartments could be used to study how plants adjust their metabolism and gene expression to accommodate the production of a new sink, and how carbon flux through one pathway can affect carbon flux through another. For example, one could study how modifying the flux of carbon to starch or lipid biosynthesis in the plastid affects the flux of carbon to acetyl-CoA and poly(3HB). Alternatively, one could study how plants adjust the activity of genes and proteins involved in isoprenoid and flavonoid biosynthesis to the creation of the poly(3HB) biosynthetic pathway in the cytoplasm, since these three pathways compete for the same building block, i. e., acetyl-CoA. 

Triterpenoid saponins are synthesized via the isoprenoid pathway.4 The first committed step in triterpenoid saponin biosynthesis involves the cyclization of 2,3-oxidosqualene to one of a number of different potential products (Fig. 5.1).4,8 Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons although lupanes are also common 4 This cyclization event forms a branchpoint with the sterol biosynthetic pathway in which 2,3-oxidosqualene is cyclized to cycloartenol in plants, or to lanosterol in animals and fungi. 

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. 

In recent years, there has been great interest in the pleiotropic effects of statins (Table 3). Many of these effects have been attributed to HMG-CoA reductase inhibition and the subsequent impairment in the synthesis of isoprenoid intermediates, which are downstream products of the cholesterol biosynthetic pathway. As a consequence, isoprenylation of proteins involved in intracellular signaling may be prevented, resulting in a variety of effects, such as an increase in bioavailability of endothelium-derived nitric oxide (53). 

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

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).

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