Nucleotide and deduced amino acid sequences of the oxidosqualene cyclase from Candida albicans

Buntel, Christopher J.; Griffin, John H.

doi:10.1021/ja00050a090

Cited by 74 publications

(37 citation statements)

References 2 publications

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“…The cyclization mechanisms of their products were extensively studied by using recombinant enzymes. Triterpene cyclases from either eukaryotes (3)(4)(5)(6)(7)(8)(9)(10) or prokaryotes (11)(12)(13)(14)(15)(16)(17) are representatives. As for diterpene cyclases, reaction mechanisms of enzymes from eukaryotes such as abietadiene synthase (18 -23), (Ϫ)-copalyl diphosphate synthase (24), and ent-kaurene synthase (25) have been recently and extensively studied.…”

mentioning

confidence: 99%

Functiona l Analysis of Eubacterial Diterpene Cyclases Responsible for Biosynthesis of a Diterpene Antibiotic, Terpentecin

Hamano

Kuzuyama²,

Itoh

et al. 2002

Journal of Biological Chemistry

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Eubacterial diterpene cyclase genes had previously been cloned from a diterpenoid antibiotic terpentecin producer (Dairi, T., Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K., and Seto, H. (2001) J. Bacteriol. 183, 6085-6094). Their products, open reading frame 11 (ORF11) and ORF12, were essential for the conversion of geranylgeranyl diphosphate (GGDP) into terpentetriene (TTE) that had the same basic skeleton as terpentecin. In this study, functional analyses of these two enzymes were performed by using purified recombinant enzymes. The ORF11 product converted GGDP into a cyclized intermediate, terpentedienol diphosphate (TDP), which was then transformed into TTE by the ORF12 product. Interestingly, the ORF12 product directly catalyzed the conversion of GGDP into three olefinic compounds. Moreover, the ORF12 product utilized farnesyl diphosphate as a substrate to give three olefinic compounds, which had the same structures as those formed from GGDP with the exception of the chain lengths. These results suggested that the ORF11 product with a DXDD motif converted GGDP into TDP by a protonation-initiated cyclization and that the ORF12 product with a DDXXD motif completed the transformation of TDP to the olefin, terpentetriene by an ionization-initiated reaction followed by deprotonation. The kinetics of the ORF12 product indicated that the affinity for TDP and GGDP were higher than that of farnesyl diphosphate and that the relative activity of the reaction converting TDP into TTE was highest among the reactions using TDP, GGDP, or farnesyl diphosphate as the substrate. These results suggested that an actual reaction catalyzed by the ORF12 was the conversion of TDP into TTE in vivo.

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confidence: 99%

Functiona l Analysis of Eubacterial Diterpene Cyclases Responsible for Biosynthesis of a Diterpene Antibiotic, Terpentecin

Hamano

Kuzuyama²,

Itoh

et al. 2002

Journal of Biological Chemistry

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“…carrying pSM61.6 synthesized 21.7 ,ug of lanosterol per mg of protein per hr, demonstrating that overexpression of ERG7 from the ADHI promoter results in formation of lanosterol synthase at a level -8 times that in the wild type. This fact and the 62% identity between S. cerevisiae ERG7 and the proposed ERG7 sequence from C. albicans (35) provide direct evidence that the latter is, in fact, the ERG7 gene.…”

Section: Resultsmentioning

confidence: 71%

“…2) predicts an 83-kDa protein 62% identical to C. albicans ERG7 (34,35) and 38% identical to A. thaliana CAS1 (27) (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

Molecular cloning, characterization, and overexpression of ERG7, the Saccharomyces cerevisiae gene encoding lanosterol synthase.

Corey

Matsuda

Bartel

1994

Proc. Natl. Acad. Sci. U.S.A.

116

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“…Recently, two OSC enzymes have been cloned and sequenced from the fungi Saccharomyces cerevisiae (15,16) and Candida albicans (17)(18)(19)). An oxidosqualene cycloartenol-cyclase was cloned and sequenced from the plantArabidopsis thaliana (20).…”

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confidence: 99%

“…Surprisingly, there were no significantly hydrophobic regions that may serve as possible membrane-spanning regions. Indeed, the EMBL neural network program (45,46) (15)(16)(17)(18)(19)(20) were all achieved by complementation of this OSC-deficient (erg7) mutant strain (33). The low copy number centromeric plasmid pYEUra3 is a modified version of AYES (pSE937) (48), which was successfully used for expression of yeast OSC in the SGL9 strain by Griffin and co-workers (16).…”

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confidence: 99%

Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA.

Abe

Prestwich

1995

Proc. Natl. Acad. Sci. U.S.A.

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A cDNA encoding rat oxidosqualene lanosterol-cyclase [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol- Oxidosqualene lanosterol-cyclase (OSC) [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol-forming), EC 5.4.99.7] catalyzes the conversion of (3S)-2,3-oxidosqualene to lanosterol, forming a total of six new carbon-carbon bonds in a single reaction (1). The regulation of OSC levels in vivo has clinical importance and has been a potential target for the design of hypercholesteremic drugs (2). The formation of lanosterol is initiated in the chair-boat-chair-like conformation of oxidosqualene, and the proton-initiated cyclization is postulated to proceed through a series of rigidly held carbocationic intermediates (1). The intermediate C-20 protosterol cation then undergoes backbone rearrangement to yield the lanosterol skeleton ( Fig. 1) (3-6). Oxidosqualene is also the precursor for a variety of other polycyclic triterpenes, and the relationship between enzyme structure and cyclization mechanism has been extensively studied (1).Several OSCs have been purified to homogeneity from vertebrate (7-9), plant (10-13), and yeast sources (14). Re

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Nucleotide and deduced amino acid sequences of the oxidosqualene cyclase from Candida albicans

Cited by 74 publications

References 2 publications

Functiona l Analysis of Eubacterial Diterpene Cyclases Responsible for Biosynthesis of a Diterpene Antibiotic, Terpentecin

Functiona l Analysis of Eubacterial Diterpene Cyclases Responsible for Biosynthesis of a Diterpene Antibiotic, Terpentecin

Molecular cloning, characterization, and overexpression of ERG7, the Saccharomyces cerevisiae gene encoding lanosterol synthase.

Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA.

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