Cycloartenol biosynthesis

Cycloartenol is an important type of stanol found in plants. The biosynthesis of cycloartenol starts from the triterpenoid squalene. It is the first precursor in the biosynthesis of other stanols and sterols, referred to as phytostanols and phytosterols in photosynthetic organisms and plants. The identities and distribution of phytostanols and phytosterols is characteristic of a plant species. One notable product of cycloartenol biosynthesis is the triterpenoid lanosterol. 

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. 

Expressed sequence tag (EST) analysis of cDNAs from specific plant tissues has proved to be a valuable tool for the identification of genes for secondary metabolite biosynthesis.36 We have used this approach to identify two distinct sequences predicted to encode OSCs from cDNA libraries from roots of diploid oat (Avena strigosa).35 One of these sequences is highly homologous to cycloartenol... 

Genetic analysis indicates that two of the 10 sad mutants of A. strigosa that we isolated represent different mutant alleles at the Sadi locus.6 These mutants accumulate radiolabelled 2,3-oxidosqualene but not p-amyrin when the roots are fed with 14C-labelled precursor mevalonic acid, suggesting that the triterpenoid pathway is blocked between 2,3-oxidosqualene and P-amyrin.34 The roots of these mutants also lack detectable P-amyrin synthase activity, but, like the wild type and the other mutants, are unimpaired in cycloartenol synthase (CS) activity and sterol biosynthesis.34 The transcript levels for AsbASl are substantially reduced in roots of sadl mutants, while AsCSl transcript levels are unaffected,35 suggesting that the sadl mutants are either mutated in the AsbASl gene itself or in a gene involved in its regulation. 

Wood SG, Gottheb D (1978) Evidence from mycelial studies for differences in the sterol biosynthetic pathway of Rhizoctonia solani and Phytophthora cinnamomi. Biochem J 170 343 Nes WD et al (1986) A comparison of cycloartenol and lanosterol biosynthesis and metabolism by the Oomycetes. Expeiientia 42 556... 

Cycloartenol (94) rather than lanosterol is thought to be the crucial triterpenoid intermediate in the biosynthesis of plant sterols, although in a chlorophyll-containing phylum there appears to be no direct correlation between ability to photosynthesize and the operation of the cycloartenol pathway.163 The cleavage of the cyclopropane ring of (94) between C-9 and C-19 should be accompanied by the incorporation of a proton at C-19, possibly from the medium. That this is the case in pea was shown164 by the incorporation of deuterium specifically at C-19 of cycloartenol obtained from... 

A24(25)-COmp0und, which is then reduced to give the saturated sterol side-chain. This route is further supported by a recent identification of stigmasta-7,24-dien-3/3-ol in higher plants.167 A similar pathway of alkylation operates for the biosynthesis of clionasterol [(24S)-(95)] from cycloartenol in the yellow-green alga Monodus subter-raneus, with the exception that direct reduction of a A24(28)-sterol [cf. (98)], rather than isomerization and then reduction, appears to occur.168... 

SpirostanolS Cardenolides, and Related Compounds.— The biosynthesis of the spirostanols diosgenin (86), yonogenin (87), and tokorogenin (88) has been studiedin Dioscorea tokoro. Cycloartenol (72), cholesterol (75), and its... 

Cucurbitacin B (99) biosynthesis has been studied in Cucurbita pepo. When [2- " C,3/ ,4/ - H]mevalonate was used, four tritium atoms were incorporated, of which one was at C-10. Using [2- C,2- H2]mevalonate, ten tritium atoms were incorporated. Thus only the expected losses from C-3, C-20, and C-22 occurred. The presence of tritium at C-8 excludes lanosterol as an intermediate. Either cycloartenol (which is present in this plant) or parkeol may be intermediates. 

This initial survey of naturally occurring cyclopropanoid metabolites raises several questions relating to the biochemistry including function and metabolism of the compounds and in particular the cyclopropyl group. In the bulk of this chapter we summarize what evidence is available on modes of biosynthesis and degradation of cyclopropyl substituents. While in several cases, e.g. in terpenoids and steroids of the cycloartenol (20) case, biogenetic tracer studies or stereochemical probes have been carried out and are quite revealing about precursor-product relationships, there are very few cases indeed where specific enzymatic catalysts have been identified, isolated, and characterized for action on specific cyclopropane substrates. 

First, we will take up cyclopropyl group formation by the rearrangement of carbon skeletons via cationic intermediates encountered in various mono- and sesquiterpenes, and also examine the illudin biosynthesis where contraction of a cyclobutyl cation to a cyclopropane has been invoked. We will then discuss the head-to-head condensation of isoprenoid alcohols at the C15 or C20 level to generate the cyclopropyl intermediates, presqualene pyrophosphate and prephytoene pyrophosphate, on the way to the C30 and C40 polyene hydrocarbons, squalene and phytoene respectively. Conversion of 2,3-oxidosqualene via common intermediate protosterol cation to cycloartenol or lanosterol represents an important pathway in which the angular methyl group participates in the three-membered ring formation. The cyclopropanation outcome of this process has been carefully studied. 

The biosynthesis of triterpenes by photosynthetic organisms proceeds via cyclization of 2,3-oxidosqualene (92) to yield cycloartenol (93), in contrast to non-photosynthetic organisms where the cyclization product is lanosterol (94) The last step in this... 

In this section we analyze information about metabolic cleavage or breakdown of cyclopropane rings in three instances the biosynthesis of irregular monoterpenes, the ringopening of cycloartenol (20) derivatives, and the metabolic opening of 1-aminocyclopropane-1-carboxylic acid (ACPC) (9) by two quite distinct fragmentation routes. We will not explicitly discuss the processing of presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) to squalene (76) and phytoene (88) respectively, since those transformations have already been dealt with in Section II. 

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