Showing papers on "Lanosterol published in 2002"
TL;DR: It is demonstrated that the evolution in the molecular chemistry from lanosterol to cholesterol is manifested in the model lipid-sterol membranes by an increase in the ability of the sterols to promote and stabilize a particular membrane phase, the liquid-ordered phase, and to induce collective order in the acyl-chain conformations of lipid molecules.
232 citations
TL;DR: The levels of the exogenous plant sterols campesterol and sitosterol were significantly elevated in the brains of APP23 animals at age 12 and 18 months, which time point coincides with abundant plaque formation.
150 citations
TL;DR: Evidence is presented that azole activity versus Saccharomyces cerevisiae is also modulated by Ca2+‐regulated signalling, and a model to explain the role of Ca2-regulated signalling in azole/terbinafine tolerance is proposed.
Abstract: The most important group of antifungals is the azoles (e.g. miconazole), which act by inhibiting lanosterol demethylase in the sterol biosynthesis pathway. Azole activity can be modulated through structural changes in lanosterol demethylase, altered expression of its gene ERG11, alterations in other sterol biosynthesis enzymes or altered expression of multidrug transporters. We present evidence that azole activity versus Saccharomyces cerevisiae is also modulated by Ca2+-regulated signalling. (i) Azole activity was reduced by the addition of Ca2+. Conversely, azole activity was enhanced by the addition of Ca2+ chelator EGTA. (ii) Three structurally distinct inhibitors (fluphenazine, calmidazolium and a W-7 analogue) of the Ca2+-binding regulatory protein calmodulin enhanced azole activity. (iii) Two structurally distinct inhibitors (cyclosporin and FK506) of the Ca2+-calmodulin-regulated phosphatase calcineurin enhanced azole activity. (iv) Strains in which the Ca2+ binding sites of calmodulin were eliminated and strains in which the calcineurin subunit genes were disrupted demonstrated enhanced azole sensitivity; conversely, a mutant with constitutively activated calcineurin phosphatase demonstrated decreased azole sensitivity. (v) CRZ1/TCN1 encodes a transcription factor regulated by calcineurin phosphatase; its disruption enhanced azole sensitivity, whereas its overexpression decreased azole sensitivity. All the above treatments had comparable effects on the activity of terbinafine, an inhibitor of squalene epoxidase within the sterol biosynthesis pathway, but had little or no effect on the activity of drugs with unrelated targets. (vi) Treatment of S. cerevisiae with azole or terbinafine resulted in transcriptional upregulation of genes FKS2 and PMR1 known to be Ca2+ regulated. A model to explain the role of Ca2+-regulated signalling in azole/terbinafine tolerance is proposed.
112 citations
TL;DR: That farnesol and lanosterol significantly suppress colonic ACF formation and crypt multiplicity strengthens the hypothesis that these agents possess chemopreventive activity against colon carcinogenesis.
91 citations
TL;DR: Cholesterol showed at all three temperatures an amplitude of its out-of-plane-motion of 1.1 nm, more than a factor of 3 higher than measured for the other two sterols, suggesting that the short alkyl chain of the cholesterol molecule may cross at high frequency the bilayer midplane, while the other three sterols remain confined within the geometrical limits of each monolayer leaflet.
Abstract: Quasi-elastic neutron scattering (QENS) was employed to study the molecular dynamics of three structurally related sterols, namely, cholesterol, lanosterol, and ergosterol. Oriented bilayers of dipalmitoylphosphatidylcholine (DPPC) were investigated at 40 mol % sterol content and at three temperatures (20, 36, and 50 °C) for two energy resolutions. Data analysis was concentrated on a direct comparison of the out-of-plane and the in-plane high-frequency motions of the three sterols in terms of their rates and amplitudes. The (spatially restricted) diffusive motion of the three sterols in the two directions was characterized by diffusion constants in the range of (5−30) × 10-12 m2 s-1, with a significantly faster rate of diffusion along the membrane normal, resulting in a diffusional anisotropy, Da. At low temperature (20 °C), cholesterol showed the highest value (Da = 4.5), while lanosterol gave the lowest one (Da = 2.0). At high temperature (50 °C), ergosterol diffusion had the highest diffusion anisotrop...
87 citations
TL;DR: In this article, the authors evaluated sterol metabolism in lymphoblast cell lines from an ABS patient without a known FGFR2 mutation and from a patient with an FGFR 2 mutation and ABS-like manifestations.
Abstract: Antley-Bixler syndrome (ABS) is a rare multiple anomaly syndrome comprising radiohumeral synostosis, bowed femora, fractures of the long bones, premature fusion of the calvarial sutures, severe midface hypoplasia, proptosis, choanal atresia, and, in some, ambiguous genitalia. Of fewer than 40 patients described to date, most have been sporadic, although reports of parental consanguinity and affected sibs of both sexes suggests autosomal recessive inheritance in some families. Known genetic causes among sporadic cases of ABS or ABS-like syndromes are missense mutations in the IgII and IgIII regions of FGFR2, although the assignment of the diagnosis of ABS to such children has been disputed. A third cause of an ABS-like phenotype is early in utero exposure to fluconazole, an inhibitor of lanosterol 14-alpha-demethylase. The fourth proposed cause of ABS is digenic inheritance combining heterozygosity or homozygosity for steroid 21-hydroxylase deficiency with effects from a second gene at an unknown locus. Because fluconazole is a strong inhibitor of lanosterol 14-alpha-demethylase (CYP51), we evaluated sterol metabolism in lymphoblast cell lines from an ABS patient without a known FGFR2 mutation and from a patient with an FGFR2 mutation and ABS-like manifestations. When grown in the absence of cholesterol to stimulate cholesterol biosynthesis, the cells from the ABS patient with ambiguous genitalia but without an FGFR2 mutation accumulated markedly increased levels of lanosterol and dihydrolanosterol. Although the abnormal sterol profile suggested a deficiency of lanosterol 14-alpha-demethylase, mutational analysis of its gene, CYP51, disclosed no obvious pathogenic mutation in any of its 10 exons or exon-intron boundaries. Sterol metabolism in lymphoblasts from the phenotypically unaffected mother was normal. Our results suggest that ABS can occur in a patient with an intrinsic defect of cholesterol biosynthesis at the level of lanosterol 14-alpha-demethylase, although the genetic nature of the deficiency remains to be determined. © 2002 Wiley-Liss, Inc.
84 citations
TL;DR: A plausible 19-step sequence of enzymatic reactions can now be written as a result of studies that have progressed from organic synthesis of the presumed intermediate, generation of the intermediate in microsomes, further enzyme conversion to cholesterol, Solubilization and purification of the membrane-bound enzyme that acts on the intermediate, and reconstitution of groups of solubilized enzymes into artificial membranes.
80 citations
TL;DR: This work describes a new class of naturally existing cytochrome P450, which will provide pivotal information for CYP structure/function in general, and examines its role in sterol biosynthesis in eukaryotes.
76 citations
TL;DR: Direct evolution was used to find cycloartenol synthase residues that affect cyclopropyl ring formation, selecting randomly generated cycloarternal synthase mutants for their ability to genetically complement a yeast strain lacking lanosterol synth enzyme.
67 citations
TL;DR: DPPC membranes doped with high concentrations of three biologically relevant sterols were studied by spectroscopic and force measurements and obtained the highest CH2-segmental molecular order and longest transverse relaxation time for cholesterol and the opposite for ergosterol.
Abstract: Lecithin (DPPC) membranes doped with high concentrations (40 mol %) of three biologically relevant sterols (cholesterol, lanosterol, and ergosterol) were studied by spectroscopic and force measurements Micropipet aspiration measurements of giant unilamellar vesicles provided the membrane area expansion modulus K on the microscopic scale while deuterium NMR experiments gave parameters such as the line shape, transverse relaxation, and molecular order, which are all based on a molecular scale at a given time resolution Micropipet experiments at 10 °C gave K values for the three samples with ergosterol > cholesterol > lanosterol From the NMR we obtained the highest CH2-segmental molecular order and longest transverse relaxation time for cholesterol and the opposite for ergosterol The lanosterol NMR parameters were found to be between those of the other two sterols but were closer to those of cholesterol The extent of deformation of the sterol-doped vesicles in the magnetic field of the NMR magnet was la
57 citations
TL;DR: It is proposed that the rapid, cytochrome P450-dependent metabolism of naturally occurring regulatory oxysterols provides a route for their deactivation so that they become incapable of affecting gene transcription.
Abstract: A ubiquitously expressed member of the cytochrome P450 superfamily, CYP51, encodes lanosterol 14alpha-demethylase, the first step in the conversion of lanosterol into cholesterol in mammals. The biosynthetic intermediates of lanosterol 14alpha-demethylation are oxysterols, which inhibit HMG-CoA reductase and sterol synthesis in mammalian cells in vitro. These oxysterols (5alpha-lanost-8-en-3beta,32-diol and 3beta-hydroxy-5alpha-lanost-8-en-32-al) are efficiently converted into cholesterol in vitro and are generally considered to be natural cholesterol precursors. When added to hepatocytes in high concentrations, besides their conversion into cholesterol, they are also rapidly metabolized into more polar sterols and into steryl esters. The 15alpha- and 15beta-hydroxy epimers of 5alpha-lanost-8-en-3beta-ol are also rapidly metabolized into more polar sterols and steryl esters but are not converted efficiently into cholesterol. Polar sterol formation from all these oxysterols is dependent on an active form of cytochrome P450. Oxysterols are potent regulators of the activities of transcription factors of the sterol regulatory element-binding protein family and of liver X-receptor alpha. It is proposed that the rapid, cytochrome P450-dependent metabolism of naturally occurring regulatory oxysterols provides a route for their deactivation so that they become incapable of affecting gene transcription. Inhibition of cytochrome P450 by the drug ketoconazole prevents the inactivation of such oxysterols, leading to a prolonged suppression of hepatic HMG-CoA reductase in vivo and in vitro.
TL;DR: To identify mutants that deprotonate differently, randomly generated mutant cycloartenol synthases were selected in a yeast lanosterol synthase mutant and two novel mutants were uncovered.
TL;DR: While regulatory mechanisms responsible for FF-MAS accumulation in the ovary are not yet established, two mechanisms contributing to production the of T-MAS in the testis have been found and potential in vivo roles of FF- MAS and T- MAS in fertilization are discussed.
TL;DR: A pathway for the conversion of lanosterol to cholesterol, based on recent results from the primary research literature, is presented and each reaction is discussed within the context of general biochemical transformations.
Abstract: Cholesterol is an important biochemical, medical, and commercial molecule. In the pathway for cholesterol biosynthesis, biochemistry textbooks discuss the synthesis of lanosterol from acetate in detail. However, the conversion of lanosterol to cholesterol is most often simply indicated as a multistep process, without elaboration. A pathway for the conversion of lanosterol to cholesterol, based on recent results from the primary research literature, is presented in this paper. Each reaction is discussed, the pathway is discussed within the context of general biochemical transformations, a summary of cholesterol homeostasis is presented, and enzyme deficiencies that give rise to diseases are given.
TL;DR: The results demonstrate that Posaconazole exerts its antifungal activity by inhibition of ergosterol biosynthesis and appears to disrupt ergosterols biosynthetic precursors by disruption of lanosterol 14alpha-demethylase.
Abstract: A liquid chromatography/mass spectrometry (LC/MS) method for separation and characterization of ergosterol biosynthetic precursors was developed to study the effect of Posaconazole on sterol biosynthesis in fungi. Ergosterol biosynthetic precursors were characterized from their electron ionization mass spectra acquired by a normal-phase chromatography, particle beam LC/MS method. Fragment ions resulting from cleavage across the D-ring and an abundant M - 15 fragment ion were diagnostic for methyl substitution at C-4 and C-14. Comparison of the sterol profile in control and treated Candida albicans incubations showed depletion of ergosterol and accumulation of C-4 and C-14 methyl-substituted sterols following treatment with Posaconazole. These C-4 and C-14 methyl sterols are known to be incapable of sustaining cell growth. The results demonstrate that Posaconazole exerts its antifungal activity by inhibition of ergosterol biosynthesis. Furthermore, Posaconazole appears to disrupt ergosterol biosynthesis by inhibition of lanosterol 14alpha-demethylase.
TL;DR: Sequence and structural homology modeling of CAS indicate that the observed product specificity-altering mutations occur both within (Tyr410Cys, Ile481Thr, and Tyr532His) and outside of (Ala469Val and His477Tyr) the cyclase active site.
Abstract: A random mutagenesis/in vivo selection approach was applied to generate and identify mutations that alter the product specificity of oxidosqualene-cycloartenol synthase (CAS) from Arabidopsis thaliana This work complements previous studies of triterpene cyclase enzymes and was undertaken to provide knowledge of the frequency and locations at which point mutations can alter cyclase product specificity Random mutations were introduced by treatment with hydroxylamine or passage through a mutator strain of bacteria Libraries of mutated plasmids carrying the cas1 gene were transformed into a cyclase-deficient strain of Saccharomyces cereVisiae (CBY57) bearing a complementing plasmid (pZS11) carrying an Erg7 gene that encodes wild-type yeast oxidosqualene-lanosterol cyclase and a URA3 marker that could be counterselected by growth in media containing 5-fluoroorotic acid (5-FOA) This allowed use of a plasmid shuffle to select for cas1 mutants that could substitute for ERG7 activity Five of 73000 transformants were observed to grow in media containing 5-FOA but lacking ergosterol pTKP5-derived plasmids isolated from these transformants were sequenced, revealing five distinct and unique point mutations: Tyr410Cys, Ala469Val, His477Tyr, Ile481Thr, and Tyr532His Analysis of the nonsaponifiable lipids from CBY57 cells expressing these mutants suggests that the Tyr410Cys and His477Tyr mutants produce lanosterol as the dominant product, whereas the Ala469Val, Ile481Thr, and Tyr532His mutants produce a mixture of lanosterol and achilleol A, a product of monocyclization Sequence and structural homology modeling of CAS indicate that the observed product specificity-altering mutations occur both within (Tyr410Cys, Ile481Thr, and Tyr532His) and outside of (Ala469Val and His477Tyr) the cyclase active site
TL;DR: Mass spectrometric fingerprint analysis of SDS-PAGE separated plasma membrane fractions combined with heterologous hyper-expression provides a convenient method for protein identification and functional evaluation of induced proteins, even in an organism where the genome sequence database is incomplete.
TL;DR: It is demonstrated for the first time that LN, a heavy-metal ion, activates the expression of the SREBP-2 and CYP51 genes without decreasing the serum total cholesterol level and it is suggested that only SRE BP-2 among SREBPs might play an important role in the LN-enhanced CYP 51 gene expression.
Abstract: Effects of lead nitrate (LN), a hepatic mitogen, on hepatic gene expressions of lanosterol 14alpha-demethylase (CYP51) and the sterol regulatory element binding proteins (SREBP-1a, SREBP-1c and SREBP-2), which are thought to be transcription factors for hepatic CYP51 gene, were examined by the methods of Northern blot and/or real time reverse transcriptase-polymerase chain reaction (RT-PCR). In both immature (4-week-old) and mature (7-week-old) rats, LN treatment resulted in definite increases in hepatic gene expression of CYP51 at 12 h and in the liver weight at 48 h. As for transcription factors for the CYP51 gene, enhanced gene expression of SREBP-2 was observed 6-12 h after LN treatment, whereas no enhanced gene expression of other SREBPs, SREBP-1a and SREBP-1c, was observed at any time after the treatment; for SREBP-1a, there was no significant change; for SREPB-1c, there was a drastic decrease. In addition, the serum total cholesterol level was increased 12 h after LN treatment to 7-week-old rats, and the increased level was maintained at least up to 48 h later. In the present study, we demonstrate for the first time that LN, a heavy-metal ion, activates the expression of the SREBP-2 and CYP51 genes without decreasing the serum total cholesterol level and further suggest that only SREBP-2 among SREBPs might play an important role in the LN-enhanced CYP51 gene expression.
TL;DR: The identification of sterol C‐24 alkylation reactions as excellent targets for the development of drugs specifically directed against this pathogen further support the identification of SAM:SMT among mammals.
Abstract: Pneumocystis is an opportunistic pathogen that can cause pneumonitis in immunodeficient people such as AIDS patients. Pneumocystis remains difficult to study in the absence of culture methods for luxuriant growth. Recombinant protein technology now makes it possible to avoid some major obstacles. The P. carinii expressed sequence tag (EST) database contains 11 entries of a sequence encoding a protein homologous to S-adenosyl-L-methionine (SAM):C-24 sterol methyl transferase (SMT), suggesting high activity of this enzyme in the organism. We sequenced the erg6 cDNA, identified the putative peptide motifs for the sterol and SAM binding sites in the deduced amino acid sequence and expressed the protein in Escherichia coli. Unlike SAM:SMT from other organisms, the P. carinii enzyme had higher affinities for lanosterol and 24-methylenelanosterol than for zymosterol, the preferred substrate in other fungi. Cycloartenol was not a productive substrate. With lanosterol and 24-methylenelanosterol as substrates, the major reaction products were 24-methylenelanosterol and pneumocysterol respectively. Thus, the P. carinii SAM:SMT catalysed the transfer of both the first and the second methyl groups to the sterol C-24 position, and the substrate preference was found to be a unique property of the P. carinii SAM:SMT. These observations, together with the absence of SAM:SMT among mammals, further support the identification of sterol C-24 alkylation reactions as excellent targets for the development of drugs specifically directed against this pathogen.
TL;DR: The annotation of the genome sequence of Streptomyces coelicolor A3(2) revealed a cytochrome P450 resembling various sterol 14alpha-demethylases (CYP51), and it is proposed that it is a member of a new CYP51 subfamily.
Abstract: The annotation of the genome sequence of Streptomyces coelicolor A3(2) revealed a cytochrome P450 (CYP) resembling various sterol 14alpha-demethylases (CYP51). The putative CYP open reading frame (SC7E4.20) was cloned with a tetrahistidine tag appended to the C-terminus and expressed in Escherichia coli. Protein purified to electrophoretic homogeneity was observed to bind the 14-methylated sterols lanosterol and 24-methylene-24,25-dihydrolanosterol (24-MDL). Reconstitution experiments with E. coli reductase partners confirmed activity in 14alpha-demethylation for 24-MDL, but not lanosterol. An S. coelicolor A3(2) mutant containing a transposon insertion in the CYP51 gene, which will abolish synthesis of the functional haemoprotein, was isolated as a viable strain, the first time a CYP51 has been identified as non-essential. The role of this CYP in bacteria is intriguing. No sterol product was detected in non-saponifiable cell extracts of the parent S. coelicolor A3(2) strain or of the mutant. S. coelicolor A3(2) CYP51 contains very few of the conserved CYP51 residues and, even though it can catalyse 14alpha-demethylation, it probably has another function in Streptomyces. We propose that it is a member of a new CYP51 subfamily.
TL;DR: The P. carinii S-adenosyl-L-methionine:sterol C-24 methyl transferase (SAM:SMT) has unique properties; it prefers lanosterol as its sterol substrate.
TL;DR: Chromatographic comparison studies lead to the conclusion that the currently studied antibodies also produce monocyclic products from the two substrates as has been formerly observed with a squalene-derived substrate.
TL;DR: The sterol composition of Pneumocystis carinii, an opportunistic pathogen responsible for life-threatening pneumonia in immunocompromised patients, was determined in this paper.
Abstract: The sterol composition of Pneumocystis carinii, an opportunistic pathogen responsible for life-threatening pneumonia in immunocompromised patients, was determined Our purpose was to identify pathway-specific enzymes to impair using sterol biosynthesis inhibitors Prior to this study, cholesterol 15 (ca 80% of total sterols), lanosterol 1, and several phytosterols common to plants (sitosterol 31, 24alpha-ethyl and campesterol, 24alpha-methyl 30) were demonstrated in the fungus In this investigation, we isolated all the previous sterols and many new compounds from P carinii by culturing the microorganism in steroid-immunosuppressed rats Thirty-one sterols were identified from the fungus (total sterol = 100 fg/cell), and seven sterols were identified from rat chow Unusual sterols in the fungus not present in the diet included, 24(28)-methylenelanosterol 2; 24(28)E-ethylidene lanosterol 3; 24(28)Z-ethylidene lanosterol 4; 24beta-ethyllanosta-25(27)-dienol 5; 24beta-ethylcholest-7-enol 6; 24beta-ethylcholesterol 7; 24beta,-ethylcholesta-5,25(27)-dienol 8; 24-methyllanosta-7-enol 9; 24-methyldesmosterol 10; 24(28)-methylenecholest-7-enol 11; 24beta-methylcholest-7-enol 12; and 24beta-methylcholesterol 13 The structural relationships of the 24-alkyl groups in the sterol side chain were demonstrated chromatographically relative to authentic specimens, by MS and high-resolution 1H NMR The hypothetical order of these compounds poses multiple phytosterol pathways that diverge from a common intermediate to generate 24beta-methyl sterols: route 1, 1 --> 2 --> 11 --> 12 --> 13; route 2, 1 --> 2 --> 9 --> 10 --> 13; or 24beta-ethyl sterols: route 3, 1 --> 2 --> 4 --> 6 --> 7; route 4, 1 --> 2 --> 5 --> 8 --> 7 Formation of 3 is considered to form an interrupted sterol pathway Taken together, operation of distinct sterol methyl transferase (SMT) pathways that generate 24beta-alkyl sterols in P carinii with no counterpart in human biochemistry suggests a close taxonomic affinity with fungi and provides a basis for mechanism-based inactivation of SMT enzyme to treat Pneumocystis pneumonia
Patent•
11 Nov 2002
TL;DR: In this article, the utilization of cholesterol, lanosterol, phytosterols and different sterols of natural and artificial origin in accordance with formula (I) for the protection of the skin against the harmful effects of UVA radiation.
Abstract: The invention relates to the utilization of cholesterol, lanosterol, phytosterols and different sterols of natural and artificial origin in accordance with formula (I) for the protection of the skin against the harmful effects of UVA radiation. The above-mentioned substances are excellent active ingredients for the production of sunscreen agents. Particularly effective are cholesterol and lanosterol, in addition to different phytosterols such as stigmasterol.
TL;DR: The cyclization of squalene epoxide to lanosterol with baker's yeast with baker’s yeast (Saccharomyces cerevisiae) can conveniently be carried out in aqueous solution with glass cored immobilisates of cells in calcium alginate, enabling the manifold use of the microorganism to obtain Lanosterol in a single biocatalytic step using the immobilisate repeatedly.
Patent•
24 Jan 2002
TL;DR: In this article, a cholesterol-lowering agent rich in natural oxygenated lanosterol derivatives originating from edible mushrooms was proposed, such an agent can be added to food products.
Abstract: The invention relates to a cholesterol-lowering agent rich in natural oxygenated lanosterol derivatives originating from edible mushrooms. Such an agent can be added to food products. The invention also relates to a method for producing one such agent.
15 Jul 2002
TL;DR: 目的研究国内临床耐氟康唑白念珠菌的吡咯类药物作用靶酶--细胞色素P-450羊毛固醇14-α脱甲基 酶
Abstract: 目的研究国内临床耐氟康唑白念珠菌的吡咯类药物作用靶酶--细胞色素P-450羊毛固醇14-α脱甲基酶的基因ERG11突变. 方法用酶消化和碱裂解法抽提基因组DNA,PCR扩增ERG11基因的读码框片段,将目的片段与PBS载体(Bluscript M13)连接,重组体转入DH5α中,从而测定序列. 结果在15株耐药菌中共发现了12个有义点突变、17个无义点突变和一个菌株的部分移码.12个有义点突变的氨基酸变异是F72L、D81G、D116E、K128T、Y132H、E266D、D294G、S361P、M374V、P386L、H400R和Q474K,突变主要靠近羧基端;而敏感株的氨基酸变异为F72L、K128T和E266D,靠近氨基端.耐药株的D294G、S361P、M374V、P386L、H400R和Q474K氨基酸变异与文献报道不同.结论耐药株和敏感株的点突变不同, D294G、S361P、M374V、P386L、H400R和Q474K变异位点可能与耐药性有关,做整段编码基因的功能表达,有助于明确变异与耐药的关系.
Journal Article•
TL;DR: It is suggested that the drug resistance is related with by the newly found alterations, including D294G, S361P, M374V, P386L, H400R, Q474K, and a frameshift.
Abstract: Objective To investigate the point mutation of the open reading frame of cytochrome P-450 lanosterol 14-α demethylase gene ERG11 Methods In order to identify such alterations, the DNA was extracted by enzyme lysis methods and the PCR was performed The PCR products were purified and cloned into PBS vector, then transformed into DH5α and sequenced Results Twenty nine point mutations were identified in this 15 resistant isolates, most of which were different from susceptible strains The mutations included 12 missense substitutions: F72L, D81G, D116E, K128T, Y132H, E266D, D294G, S361P, M374V, P386L, H400R, and Q474K, of which 6 had not been described previously (D294G, S361P, M374V, P386L, H400R, and Q474K) The other mutations included a frameshift, and 17 silent mutations Conclusions The point mutation of resistant isolate is different from that of the susceptible isolate It is suggested that the drug resistance is related with by the newly found alterations, including D294G, S361P, M374V, P386L, H400R, Q474K, and a frameshift
TL;DR: This chapter reviews the progress that has been made in the characterization of the enzymes and genes involved in the synthesis of triterpenoid saponins, indicating that avenacins contribute to disease resistance in oat and AsbAS1 and other as yet uncharacterized genes required for sap onin biosynthesis have potential for the development of plants with altered saponin content through metabolite engineering.
Abstract: Publisher Summary This chapter reviews the progress that has been made in the characterization of the enzymes and genes involved in the synthesis of triterpenoid saponins. The enzyme is unusual in that it is more closely related to lanosterol synthases from animals and fungi than to other oxidosqualene cyclases (triterpenoid synthases or cycloartenol synthases) from plants. β-amyrin synthase (AsbAS1) is required for the synthesis of triterpenoid avenacin saponins and for resistance to a variety of pathogens, indicating that avenacins contribute to disease resistance in oat. AsbAS1 and other as yet uncharacterized genes required for saponin biosynthesis have potential for the development of plants with altered saponin content through metabolite engineering. In some cases, enhanced levels of saponins or the synthesis of novel saponins may be beneficial (for example, for drug production or improved disease resistance), while in others the objective may be to reduce the content of undesirable saponins (such as those associated with antinutritional effects in legumes).
Patent•
11 Dec 2002
TL;DR: The present invention provides a compound of formula (I) Compounds, diseases associated with 2,3-oxidosqualene lanosterol cyclase for the treatment and / or prophylaxis of impaired glucose tolerance and diabetes.
Abstract: The present invention provides a compound of formula (I) Compounds, diseases associated with 2,3-oxidosqualene lanosterol cyclase, for example, hypercholesterolemia, hyperlipidemia, arteriosclerosis, vascular diseases, mycoses, parasite infections, gallstones, tumors and / or excess treatment and / or prevention of a proliferative disorder, as well as for the treatment and / or prophylaxis of impaired glucose tolerance and diabetes.