Activity of <i>Pichia pastoris</i> alternative <i>cis</i>‐prenyltransferase is correlated with proliferation of peroxisomes

Skoneczny, Marek; Kłudkiewicz, Barbara; Świeżewska, Ewa; Szkopińska, Anna

doi:10.1016/j.cellbi.2005.09.006

Cited by 6 publications

(5 citation statements)

References 19 publications

(48 reference statements)

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“…peroxisomal CPT and PPRD, IPP and oligoprenyl diphosphate transporters). Besides plastids and the endoplasmic reticulum, postulated earlier to harbor CPTs (Skorupinska-Tudek et al, 2008), plant peroxisomes also could possess their own CPT, as was observed in mammals and yeast (Ericsson et al, 1992;Skoneczny et al, 2006). Moreover, the existence of the peroxisomal pathway converting MVA to IPP in mammals and plants (Thompson et al, 1987;Simkin et al, 2011) further supports this concept.…”

Section: Discussionsupporting

confidence: 58%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (Arabidopsis thaliana). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes.Isopentenyl diphosphate (IPP), the building block of isoprenoids, the most numerous class of secondary metabolites, is derived in plants from two pathways operating in parallel: the cytoplasmic mevalonate (MVA) and the plastidic methylerythritol phosphate (MEP) pathways (Rohmer, 1999;Pulido et al., 2012).Analysis of over 130 isoprenoids has shown that, in angiosperms under standard growth conditions, carotenoids and chlorophyll phytyl chains on the one hand and phytosterols on the other are made nearly exclusively via a single pathway (MEP and MVA, respectively), while numerous other isoprenoids, including dolichols (Dols; Skorupinska-Tudek et al., 2008), are of mixed origin (Hemmerlin et al., 2012).The cooperation of the two pathways (often called cross talk) is considered essential for plant adaptive responses to biotic and abiotic stresses. Consequently, their relative contributions to the formation of IPP are modulated, and the expression of particular genes of the MVA and MEP pathways is frequently correlated with stress (pathogen attack, elicitation, wounding, etc.;Hemmerlin et al., 2012) or plant development (Opitz et al., 2014). Interestingly, the effect of stress on the regulation of the MEP-MVA balance has so far been analyzed only qualitatively.Several methodologies have been employed to unravel the relative contributions of the MVA and MEP pathways to isoprenoids, such as metabolic labeling with isotopically labeled precursors (stable isotopes or radioisotopes were used), followed by structural analysis of the product of interest or blockage of the pathway (chemical, with pathway-specific inhibitors, or genetic), followed by quantification of the isoprenoid intermediates and/or end products. The advantages

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Section: Discussionsupporting

confidence: 58%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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“…This step is called elongation and in animals occurs in the endoplasmic reticulum (ER) where its downstream products dolichyl phosphates (Dol-Ps) serve as lipid oligosaccharide carrier for protein N- glycosylation, C - and O -mannosylation and glycosylphosphatidylinositol (GPI) synthesis (reviewed in 29 ). In other organisms, cis -polyisoprenoid synthesis also occurs in peroxisomes (rat 30 , yeast 31 ), lipid droplets (yeast 20 , 32 ) and chloroplasts (plants, cyanobacteria 21 , 33 ). The postulated final steps of cis -polyisoprenoid biosynthesis involve dephosphorylation of PDP to polyprenol followed by reduction of the α-isoprene unit by polyprenol reductase (PPRD), also called SRD5A3 or DFG10 in mammals and yeast, respectively (Fig.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum

Zimbres

Valenciano

Merino

et al. 2020

Sci Rep

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the cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor polyprenol, are unusual in eukaryotic cells. Our metabolomics studies revealed that cis-polyisoprenoids are more diverse in the malaria parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite's development. Moreover, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite. Malaria is caused by protozoan parasites of the genus Plasmodium and most cases of life-threatening malaria are attributable to infection with Plasmodium falciparum. The parasite has a complex life cycle that involves the human host and its vector, the Anopheles mosquitoes. All clinical features are caused during the asexual intraerythrocytic life cycle due to the repeated invasion of human red blood cells (RBCs). The asexual intraerythrocytic developmental cycle of P. falciparum lasts around 48 h, during which the parasite progresses through four morphologically different stages: ring, trophozoite, and schizont stages, ending with rupture of the erythrocyte and release of merozoites that will invade new erythrocytes. Transmission of the malaria parasite requires development of male and female gametocytes (gametocytogenesis), which are ingested by female mosquitoes during a blood meal and undergo sexual reproduction in the mosquito's midgut. Nondividing P. falciparum gametocytes take between 10 and 12 days to fully mature and progress through five morphologically distinct forms (stages I to V), which are different from other Plasmodium species. During their complex life cycle malaria parasites encounter different nutritional environments within and between hosts. The presence of de novo and salvage pathways gives parasites a great metabolic flexibility to cope with those changes 1,2. For example, mature RBCs are capable of only a few metabolic functions since transcription and translation is not present in these cells. However, a wide variety of metabolites are available to the parasite in the human plasma 3. Among the metabolic pathways that become inactive in mature RBCs is the mevalonate pathway which synthesizes the isoprenoid building blocks isopentenyl diphosphate (IPP) and d...

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“…This step is called elongation and in animals occurs in the endoplasmic reticulum (ER) where its downstream products dolichyl phosphates (Dol-Ps) serve as lipid oligosaccharide carrier for protein N-glycosylation, C-and O-mannosylation and glycosylphosphatidylinositol (GPI) synthesis (reviewed in 28 ). In other organisms, cis-polyisoprenoid synthesis also occurs in peroxisomes (rat 29 , yeast 30 ), lipid droplets (yeast 20,31 ) and chloroplasts (plants, cyanobacteria 21,32 ). The postulated final steps of cis-polyisoprenoid biosynthesis involve dephosphorylation of PDP to polyprenol followed by reduction of the a-isoprene unit by polyprenol reductase (PPRD), also called SRD5A3 or DFG10 in mammals and yeast, respectively ( Fig.…”

mentioning

confidence: 99%

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

Zimbres¹,

Valenciano²,

Merino³

et al. 2019

Preprint

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The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Polyprenols have been hardly detectable in eukaryotic cells under normal conditions with the exception of plants and sporulating yeast. Our metabolomics studies revealed that cis-polyisoprenoids are more prevalent and diverse in the parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was also observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite's development. In addition, we confirmed the presence of an active cisprenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite. Isotopic labeling and metabolomic analyses of a conditional mutant of PfCPT or PfPPRD suggest that polyprenols may be able to substitute dolichols in their biological functions when dolichol synthesis is impaired in Plasmodium.Malaria is caused by protozoan parasites of the genus Plasmodium and most cases of lifethreatening malaria are attributable to infection with Plasmodium falciparum. The parasite has a complex life cycle that involves the human host and its vector, the Anopheles mosquitoes. All clinical features are caused during the asexual intraerythrocytic life cycle due to the repeated invasion of human red blood cells (RBCs). The asexual intraerythrocytic developmental cycle of P. falciparum lasts around 48 h, during which the parasite progresses through four morphologically different stages: ring, trophozoite, and schizont stages, ending with rupture of the erythrocyte and release of merozoites that will invade new erythrocytes. Transmission of the malaria parasite requires development of male and female gametocytes (gametocytogenesis), which are ingested by female mosquitoes during a blood meal and undergo sexual reproduction in the mosquito's midgut. Nondividing P. falciparum gametocytes take between 10 and 12 2 days to fully mature and progress through five morphologically distinct forms (stages I to V), which are different from other Plasmodium species.During their complex life cycle malaria parasites encounter different nutritional environments within and between hosts. The presence of de novo and salvage pathways gives parasites a great metabolic flexibility to cope with those changes 1,2 . For example, mature RBCs are capable of only a few metabolic functions since transcription and translation is not present in these cells. However, a wide variety of metabolites are available to the parasite i...

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Activity of Pichia pastoris alternative cis‐prenyltransferase is correlated with proliferation of peroxisomes

Cited by 6 publications

References 19 publications

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

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