79-63-0Relevant articles and documents
Efficient cyclization of squalene epoxide to lanosterol with immobilized cells of baker's yeast
Rotthaus, Olaf,Demuth, Martin
, p. 7291 - 7293 (2002)
The cyclization of squalene epoxide to lanosterol with baker's yeast (Saccharomyces cerevisiae) can conveniently be carried out in aqueous solution with glass cored immobilisates of cells in calcium alginate. This enables the manifold use of the microorganism to obtain lanosterol in a single biocatalytic step using the immobilisates repeatedly.
Partial purification and characterization of oxidosqualene-lanosterol cyclase from baker's yeast
Hoshino,Williams,Chung,Scott
, p. 5925 - 5932 (1991)
Partial (120-fold) purification of oxidosqualene-lanosterol cyclase from yeast is described. The enzyme derived from the microsomal fraction converts 1 mM S-squalene oxide to lanosterol in 5 h and has a pH optimum of 6.2, lower than that (pH 7.2) of the hog-liver cyclase catalyzing the same reaction. Although the yeast cyclase is stimulated by high concentrations of potassium phosphate buffer, high concentrations of potassium or sodium chloride inhibit activity. The concentration range of Triton X-100 for optimal activity is 0.7-1.2%.
NMR Biochemical Assay for Oxidosqualene Cyclase: Evaluation of Inhibitor Activities on Trypanosoma cruzi and Human Enzymes
Tani, Osamu,Akutsu, Yukie,Ito, Shinji,Suzuki, Takayuki,Tateishi, Yukihiro,Yamaguchi, Tomohiko,Niimi, Tatsuya,Namatame, Ichiji,Chiba, Yasunori,Sakashita, Hitoshi,Kubota, Tomomi,Yanagi, Tetsuo,Mizukami, Shusaku,Hirayama, Kenji,Furukawa, Koji,Yamasaki, Kazuhiko
, p. 5047 - 5053 (2018/05/29)
Oxidosqualene cyclase (OSC), a membrane-associated protein, is a key enzyme of sterol biosynthesis. Here we report a novel assay for OSC, involving reaction in aqueous solution, NMR quantification in organic solvent, and factor analysis of spectra. We evaluated one known and three novel inhibitors on OSC of Trypanosoma cruzi, a parasite causative of Chagas disease, and compared their effects on human OSC for selectivity. Among them, one novel inhibitor showed a significant parasiticidal activity.
A well-defined monomeric aluminum complex as an efficient and general catalyst in the Meerwein-Ponndorf-Verley reduction
McNerney, Brian,Whittlesey, Bruce,Cordes, David B.,Krempner, Clemens
supporting information, p. 14959 - 14964 (2015/01/08)
The metal-catalyzed Meerwein-Ponndorf-Verley (MPV) reduction allows for the mild and sustainable reduction of aldehydes and ketones but has not found widespread application in organic synthesis due to the high catalyst loading often required to obtain satisfactory yields of the reduced product. We report here on the synthesis and structure of a sterically extremely overloaded siloxide-supported aluminum isopropoxide capable of catalytically reducing a wide range of aldehydes and ketones (52 examples) in excellent yields under mild conditions and with low catalyst loadings. The unseen activity of the developed catalyst system in MPV reductions is due to its unique monomeric nature and the neutral donor isopropanol weakly coordinating to the aluminum center. The present work implies that monomeric aluminum alkoxide catalysts may be attractive alternatives to transition-metalbased systems for the selective reduction of aldehydes and ketones to primary and secondary alcohols.
The cysteine 703 to isoleucine or histidine mutation of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae generates an iridal-type triterpenoid
Chang, Cheng-Hsiang,Chen, Yi-Chi,Tseng, Sheng-Wei,Liu, Yuan-Ting,Wen, Hao-Yu,Li, Wen-Hsuan,Huang, Chiao-Ying,Ko, Cheng-Yu,Wang, Tsai-Ting,Wu, Tung-Kung
, p. 2376 - 2381,6 (2020/08/20)
The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7C703I/H) generates an unusual truncated bicyclic rearranged intermediate, (8R,9R,10R)-polypoda-5,13E, 17E,21-tetraen-3β-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17α/β exocyclic hydrocarbon side chain, rearranged tetracyclic, and chair-chair-chair tricyclic intermediates (compounds 3-9), were also isolated from the ERG7C703X site-saturated mutations or the ERG7F699T/C703I double mutation, indicating the functional role of the Cys703 residue in stabilizing the bicyclic C-8 cation and the rearranged intermediate or interacting with Phe699, and opened a new avenue of engineering ERG7 for producing biological active agents.
Sterol C24-methyltransferase: Physio- and stereo-chemical features of the sterol C3 group required for catalytic competence
Howard, Alicia L.,Liu, Jialin,Elmegeed, Gamal A.,Collins, Emily K.,Ganatra, Kalgi S.,Nwogwugwu, Chizaram A.,Nes, W. David
body text, p. 43 - 50 (2012/08/07)
Sterol C24-methyltransferases (24-SMTs) catalyze the electrophilic alkylation of Δ24-sterols to a variety of sterol side chain constructions, and the C3- moiety is the primary determinant for substrate binding by these enzymes. To determine what specific structural features of the C3-polar group ensure sterol catalysis, a series of structurally related C3-analogs of lanosterol that differed in stereochemistry, bulk and electronic properties were examined against the fungal 24-SMT from Paracoccidioides brasiliensis (Pb) which recognize lanosterol as the natural substrate. Analysis of the magnitude of sterol C24-methylation activity (based on the kinetic constants of Vmax/Km and product distributions determined by GC-MS) resulting from changes at the C3-position in which the 3β-OH was replaced by 3α-OH, 3β-acetyl, 3-oxo, 3-OMe, 3β-F, 3β-NH2 (protonated species) or 3H group revealed that lanosterol and five substrate analogs were catalyzed and yielded identical side chain products whereas neither the 3H- or 3α-OH lanosterol derivatives were productively bound. Taken together, our results demonstrate a chemical complementarity involving hydrogen bonding formation of specific active site contacts to the nucleophilic C3-group of sterol is required for proper orientation of the substrate C-methyl intermediate in the activated complex.
PROCESS FOR THE PREPARATION OF LANOSTA-8-ENE COMPOU
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Page/Page column 4-5, (2010/04/03)
The present invention concerns a process for the preparation of lanosta-8-ene compounds having lanosta-8-ene-7-one or lanosta-8-ene-7-ol compounds as starting material.
Protostadienol synthase from Aspergillus fumigatus: Functional conversion into lanosterol synthase
Kimura, Miki,Kushiro, Tetsuo,Shibuya, Masaaki,Ebizuka, Yutaka,Abe, Ikuro
experimental part, p. 899 - 902 (2011/04/16)
Oxidosqualene:protostadienol cyclase (OSPC) from the fungus Aspergillus fumigatus, catalyzes the cyclization of (3S)-2,3-oxidosqualene into protosta-17(20)Z,24-dien-3β-ol which is the precursor of the steroidal antibiotic helvolic acid. To shed light on the structure-function relationship between OSPC and oxidosqualene:lanosterol cyclase (OSLC), we constructed an OSPC mutant in which the C-terminal residues 702APPGGMR708 were replaced with 702NKSCAIS708, as in human OSLC. As a result, the mutant no longer produced the protostadienol, but instead efficiently produced a 1:1 mixture of lanosterol and parkeol. This is the first report of the functional conversion of OSPC into OSLC, which resulted in a 14-fold decrease in the Vmax/KM value, whereas the binding affinity for the substrate did not change significantly. Homology modeling suggested that stabilization of the C-20 protosteryl cation by the active-site Phe701 through cation-π interactions is important for the product outcome between protostadienol and lanosterol.
Alteration of the substrate's prefolded conformation and cyclization stereochemistry of oxidosqualene-lanosterol cyclase of saccharomyces cerevisiae by substitution at Phenylalanine 699
Wu, Tung-Kung,Chang, Cheng-Hsiang,Wen, Hao-Yu,Liu, Yuan-Ting,Li, Wen-Hsuan,Wang, Tsai-Ting,Shie, Wen-Shiang
scheme or table, p. 500 - 503 (2010/05/18)
[Chemical equaction presented] The Saccharomyces cerevisiae ERG7 Phe699 mutants produced one chair-chair-chair (C-C-C) and two chair-boat-chair (C-B-C) truncated tricyclic compounds, one tetracyclic 17α-exocyclic unrearranged intermediate, and
Differential stereocontrolled formation of tricyclic triterpenes by mutation of tyrosine 99 of the oxidosqualene-lanosterol cyclase from saccharomyces cerevisiae
Wu, Tung-Kung,Li, Wen-Hsuan,Chang, Cheng-Hsiang,Wen, Hao-Yu,Liu, Yuan-Ting,Chang, Yi-Chun
experimental part, p. 5731 - 5737 (2010/03/01)
The function of the Tyr99 residue from Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase (ERG7) was analyzed by constructing deletion, and site-saturated mutants. Two truncated intermediates, (13αH)- isomalabarica-14Z,17E,21-trien-3βol and. (13αH)
