Oxidosqualene Cyclase Residues that Promote Formation of Cycloartenol, Lanosterol, and Parkeol

Meyer, Michelle M.; Segura, Michael J. R.; Wilson, William K.; Matsuda, Seiichi P. T.

doi:10.1002/1521-3757(20001117)112:22<4256::aid-ange4256>3.0.co;2-d

Cited by 19 publications

(12 citation statements)

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“…It has been shown that wild-type Arabidopsis CAS, expressed in a yeast mutant, is able to produce 1% parkeol, but not lanosterol (<0.1%) [28]. Moreover, the possibility to generate an enzyme that makes parkeol as its major product from either CAS [28,59,60] or lanosterol synthase [61,62] has been reported. As an example, the work by Segura et al [60] has emphasized the critical role played by His477, which is strictly conserved in all CAS.…”

Section: Origin Of the Structural Diversity Of Triterpenoids In Olivementioning

confidence: 99%

Formation of Triterpenoids throughout Olea europaea Fruit Ontogeny

Stiti

Triki

Hartmann

2007

Lipids

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Drupes were handpicked from olive (Olea europaea L.) trees, cv chemlali, at 13 distinct stages of fruit development, referred to as weeks after flowering (WAF), and analyzed for their free and esterified sterols and triterpenoids content. These two classes of compounds are synthesized via the acetate/mevalonate pathway and share common precursors up to oxidosqualene (OS). Cyclization of OS in either cycloartenol or beta-amyrin constitutes a branch point between primary (sterol pathway) and secondary (triterpenoid pathway) metabolisms. At the onset of fruit development, i.e., between 12 and 18 WAF, drupes were found to contain high amounts of alpha- and beta-amyrins as well as more-oxygenated compounds such as triterpenic diols (erythrodiol and uvaol) and acids (oleanolic, ursolic and maslinic acids). Concomitantly, sterol precursors were barely detectable. From 21 WAF, when the olive fruit reached its final size and began to turn from green to purple, alpha- and beta-amyrins were no longer present, while 4,4-dimethyl- and 4alpha-methylsterols started to be formed, indicating a redirection of the carbon flux from the triterpenoid pathway towards the sterol pathway. Between 21 and 30 WAF, sterol end products, mainly represented by sitosterol, progressively accumulated and triterpenic diols were replaced by triterpenic acids, essentially maslinic acid. Interestingly, the developing olive fruit was found to accumulate significant amounts of parkeol as an ester conjugate. Whatever the stage of development, triterpenoids represent the major triterpenic compounds of the olive fruit.

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Section: Origin Of the Structural Diversity Of Triterpenoids In Olivementioning

confidence: 99%

Formation of Triterpenoids throughout Olea europaea Fruit Ontogeny

Stiti

Triki

Hartmann

2007

Lipids

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“…OSC have been purified and cloned from different species: Candida albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe among the fungi; higher plants; the rat; the pig; and human (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). SHC from Alicyclobacillus acidocaldarius has recently been overexpressed in Escherichia coli, purified, and crystallized (18)(19)(20).…”

mentioning

confidence: 99%

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Rocco

Bosso

Viola

et al. 2003

Lipids

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Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene (OS) and conjugated and non-conjugated phenylthio derivatives of OS were obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalene-hopene cyclase (SHC) (EC 5.4.99.-), contain the reactive function adjacent to carbons involved in the formation of the third and the fourth cycle during OS cyclization. All the new compounds are inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas most of the phenylthio derivatives were especially active toward SHC.

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“…All other eukaryotes that have been examined in this regard (at least members of the higher plants, green and red algae, amoebozoa, diatoms, euglenids and heterolobosea) make cycloartenol as their protosterol. Site-directed mutagenesis experiments, notably those of Matsuda and co-workers (Meyer et al 2000Joubert et al 2001;Segura et al 2002;Lodeiro et al 2004) have indicated the key residues that control the product profile of OSCs, including T381, C449 and V453. From analysis of the crystal structure, each appears to affect the position of the catalytic base dyad H232-Y503.…”

Section: Resultsmentioning

confidence: 99%

Molecular biogeochemistry of modern and ancient marine microbes

Waldbauer¹

2010

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Biological activity has shaped the surface of the earth in numerous ways, but life's most pervasive and persistent global impact has been the secular oxidation of the surface environment. Through primary production -the biochemical reduction of carbon dioxide to synthesize biomass -large amounts of oxidants such as molecular oxygen, sulfate and ferric iron have accumulated in the ocean, atmosphere and crust, fundamentally altering the chemical environment of the earth's surface. This thesis addresses aspects of the role of marine microorganisms in driving this process. In the first section of the thesis, biomarkers (hydrocarbon molecular fossils) are used to investigate the early history of microbial diversity and biogeochemistry. Molecular fossils from the Transvaal Supergroup, South Africa, document the presence in the oceans of a diverse microbiota, including eukaryotes, as well as oxygenic photosynthesis and aerobic biochemistry, by ca. 2.7Ga. Experimental study of the oxygen requirements of steroid biosynthesis suggests that sterane biomarkers in late Archean rocks are consistent with the persistence of microaerobic surface ocean environments long before the initial oxygenation of the atmosphere. In the second part, using Prochlorococcus (a marine cyanobacterium that is the most abundant primary producer on earth today) as a model system, we explored how microbes use the limited nutrient resources available in the marine environment to make the protein catalysts that enable primary production. Quantification of the Prochlorococcus proteome over the diel cell-division cycle reveals that protein abundances are distinct from transcript-level dynamics, and that small temporal shifts in enzyme levels can redirect metabolic fluxes. This thesis illustrates how molecular techniques can contribute to a systems-level understanding of biogeochemical processes, which will aid in reconstructing the past of, and predicting future change in, earth surface environments. ACKNOWLEDGMENTSI have incurred many debts of gratitude and appreciation over the course of this work. None are greater than those to my advisors, Penny Chisholm and Roger Summons, who allowed and enabled me to pursue such a wide range of scientific interests and offered their help and advice every step of the way. I have been very lucky to have had the chance to learn so much during my Ph.D., and none of that would have been possible without their guidance and support.I have also had the great fortune to know and work with all the members of the Chisholm and Summons labs, who have made this an enjoyable and rewarding place to be. I am especially grateful to Laura Sherman for her skill and dedication in analyzing biomarkers in the late Archean cores -it was truly getting blood from a stone. I was lucky to collaborate with Sébastien Rodrigue, whose expertise and collegiality made the diel experiment even more fruitful than I could have hoped. IntroductionThe coevolution of life and earth surface environments is central to the history and functionin...

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Oxidosqualene Cyclase Residues that Promote Formation of Cycloartenol, Lanosterol, and Parkeol

Abstract: We are grateful to Bridget M. Joubert for advice regarding mutagenesis. We thank Elizabeth A. Hart for an authentic parkeol standard, and for chromatographic and spectroscopic information.

Cited by 19 publications

References 20 publications

Formation of Triterpenoids throughout Olea europaea Fruit Ontogeny

Formation of Triterpenoids throughout Olea europaea Fruit Ontogeny

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Molecular biogeochemistry of modern and ancient marine microbes

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