The Arabidopsis thaliana FPS1 Gene Generates a Novel mRNA That Encodes a Mitochondrial Farnesyl-diphosphate Synthase Isoform

Cunillera, Núria; Boronat, Albert; Ferrer, Albert

doi:10.1074/jbc.272.24.15381

Cited by 158 publications

(132 citation statements)

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“…We do not know if, as for the Arabidopsis fps1 gene, differential transcription leads to multiple isoforms with alternate locations (Cunillera et al, 1997). For the maize long clone pME14D1184 (compare with Fig.…”

Section: Discussionmentioning

confidence: 99%

Maize cDNAs Expressed in Endosperm Encode Functional Farnesyl Diphosphate Synthase with Geranylgeranyl Diphosphate Synthase Activity

et al. 2006

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Isoprenoids are the most diverse and abundant group of natural products. In plants, farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are precursors to many isoprenoids having essential functions. Terpenoids and sterols are derived from FPP, whereas gibberellins, carotenoids, casbenes, taxenes, and others originate from GGPP. The corresponding synthases (FPP synthase [FPPS] and GGPP synthase [GGPPS]) catalyze, respectively, the addition of two and three isopentenyl diphosphate molecules to dimethylallyl diphosphate. Maize (Zea mays L. cv B73) endosperm cDNAs encoding isoprenoid synthases were isolated by functional complementation of Escherichia coli cells carrying a bacterial gene cluster encoding all pathway enzymes needed for carotenoid biosynthesis, except for GGPPS. This approach indicated that the maize gene products were functional GGPPS enzymes. Yet, the predicted enzyme sequences revealed FPPS motifs and homology with FPPS enzymes. In vitro assays demonstrated that indeed these maize enzymes produced both FPP and GGPP and that the N-terminal sequence affected the ratio of FPP to GGPP. Their functionality in E. coli demonstrated that these maize enzymes can be coupled with a metabolon to provide isoprenoid substrates for pathway use, and suggests that enzyme bifunctionality can be harnessed. The maize cDNAs are encoded by a small gene family whose transcripts are prevalent in endosperm beginning mid development. These maize cDNAs will be valuable tools for assessing the critical structural properties determining prenyl transferase specificity and in metabolic engineering of isoprenoid pathways, especially in cereal crops.

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Section: Discussionmentioning

confidence: 99%

Maize cDNAs Expressed in Endosperm Encode Functional Farnesyl Diphosphate Synthase with Geranylgeranyl Diphosphate Synthase Activity

et al. 2006

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“…Both FPPS and GGPPS have been found in different cellular compartments, namely the cytosol (34,35), mitochondria (35,36), plastids in plants (35,37), and the peroxisome in animals (38). The presence of ubiquinol-cytochrome c oxidoreductase, which couples the transfer of electrons from ubiquinol (QH 2 ) to cytochrome c, in T. gondii mitochondria, and the inhibition of respiration and collapse of mitochondrial membrane potential by antimycin A and cyanide (39) support the presence of ubiquinone in the T. gondii mitochondrion.…”

Section: Table 2 Kinetic Parameters Of Tgfppsmentioning

confidence: 99%

The Farnesyl-diphosphate/Geranylgeranyl-diphosphate Synthase of Toxoplasma gondii Is a Bifunctional Enzyme and a Molecular Target of Bisphosphonates

Ling

Miranda

et al. 2007

Journal of Biological Chemistry

115

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Farnesyl-diphosphate synthase (FPPS) catalyzes the synthesis of farnesyl diphosphate, an important precursor of sterols, dolichols, ubiquinones, and prenylated proteins. We report the cloning and characterization of two Toxoplasma gondii farnesyl-diphosphate synthase (TgFPPS) homologs. A single genetic locus produces two transcripts, TgFPPS and TgFPPSi, by alternative splicing. Both isoforms were heterologously expressed in Escherichia coli, but only TgFPPS was active. The protein products predicted from the nucleotide sequences have 646 and 605 amino acids and apparent molecular masses of 69.5 and 64.5 kDa, respectively. Several conserved sequence motifs found in other prenyl-diphosphate synthases are present in both TgFPPSs. TgFPPS was also expressed in the baculovirus system and was biochemically characterized. In contrast to the FPPS of other eukaryotic organisms, TgFPPS is bifunctional, catalyzing the formation of both farnesyl diphosphate and geranylgeranyl diphosphate. TgFPPS localizes to the mitochondria, as determined by the co-localisation of the affinity-purified antibodies against the protein with MitoTracker, and in accord with the presence of an N-terminal mitochondria-targeting signal in the protein. This enzyme is an attractive target for drug development, because the order of inhibition of the enzyme by a number of bisphosphonates is the same as that for inhibition of parasite growth. In summary, we report the first bifunctional farnesyl-diphosphate/geranylgeranyldiphosphate synthase identified in eukaryotes, which, together with previous results, establishes this enzyme as a valid target for the chemotherapy of toxoplasmosis.Toxoplasma gondii is a pathogenic protozoan parasite that infects a wide range of vertebrate hosts, including humans. T. gondii has been recognized as a major opportunistic pathogen of fetuses from recently infected mothers and of immunocompromised patients, i.e. those with AIDS. Toxoplasmic encephalitis is associated with high mortality and morbidity and is one of the most common opportunistic infections of the central nervous system in human immunodeficiency virus-infected patients (1). The chemotherapy for toxoplasmosis is not ideal especially for the AIDS patient because there is relapse of the infection if the treatment is halted because of intolerance of the patient to the side effects. Almost all the drugs in use have toxicity associated with their continued use. In addition, most of the recommended treatments do not have an effect on the slow growing bradyzoite forms.Isoprenoids are the most diverse and abundant compounds occurring in nature. Many types of isoprenoids (e.g. steroids, cholesterol, retinoids, carotenoids, ubiquinones, and prenyl groups bound to proteins) are essential components of the cellular machinery of all organisms because of their roles in a variety of biological processes. Despite their structural and functional variety, all isoprenoids derive from a common precursor, isopentenyl diphosphate (IPP), 2 and its isomer, dimethylallyl diphosphate (...

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“…Two well characterized Arabidopsis FPP synthases were localized to the cytoplasm and mitochondria (46). Therefore, FPP in plastids could possibly be synthesized as a leaked side product formed either by geranyl or geranylgeranyl-diphosphate synthases because in Arabidopsis both these enzymes were found in this compartment (47,48); however, plastidial localization of farnesyl-diphosphate synthase has also been postulated (49).…”

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confidence: 99%

Contribution of the Mevalonate and Methylerythritol Phosphate Pathways to the Biosynthesis of Dolichols in Plants

Skorupińska-Tudek

Poznański

Wójcik

et al. 2008

Journal of Biological Chemistry

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Plant isoprenoids are derived from two biosynthetic pathways, the cytoplasmic mevalonate (MVA) and the plastidial methylerythritol phosphate (MEP) pathway. In this study their respective contributions toward formation of dolichols in Coluria geoides hairy root culture were estimated using in vivo labeling with 13 C-labeled glucose as a general precursor. NMR and mass spectrometry showed that both the MVA and MEP pathways were the sources of isopentenyl diphosphate incorporated into polyisoprenoid chains. The involvement of the MEP pathway was found to be substantial at the initiation stage of dolichol chain synthesis, but it was virtually nil at the terminal steps; statistically, 6 -8 isoprene units within the dolichol molecule (i.e. 40 -50% of the total) were derived from the MEP pathway. These results were further verified by incorporation of Polyisoprenoid alcohols together with sterols and quinone side chains constitute three main branches of terpene products originating from farnesyl diphosphate (FPP) 4 (1). These linear five-carbon unit polymers are divided into two groups, i.e. polyprenols and dolichols, according to the hydrogenation status of the ␣-terminal isoprene unit (dolichol structure is shown in Fig. 1). In cells, polyprenols and dolichols are always found as mixtures of prenologues, and data collected so far show polyprenols to be typical for bacteria and plants, whereas dolichols are generally attributed to animals and yeast (2). Nevertheless, it should be remembered that dolichols are the predominant form in some plant organs like roots (3). Data on the occurrence and functions of polyisoprenoids are summarized in recently published reviews (4, 5). The formation of the polyisoprenoid chain, starting from the -end of the molecule (Fig. 1), proceeds in a biphasic manner with farnesyl-diphosphate synthase responsible for the synthesis of the all-trans-FPP (three isoprene units of -t 2 structure, t stands for trans-isoprene unit), and its further elongation by cis-prenyltransferase. The latter enzyme, cloned from several prokaryotic and eukaryotic organisms (see Refs. 6, 7 and references therein), including Arabidopsis thaliana (8,9) and Hevea brasiliensis (10), utilizes isopentenyl diphosphate (IPP) for elongation of FPP up to the desired chain length, thus producing a family of polyprenyl diphosphates (n isoprene units of -t 2 -c n-3 structure, c stands for cis-isoprene unit), which are subsequently converted to polyprenols or dolichols according to the "tissue-specific requirements" by a still unknown mechanism.In plant cells two pathways are known to produce IPP utilized by numerous enzymes to finally give more than 50,000 different isoprenoid structures, the mevalonate pathway (MVA) and the mevalonate-independent methylerythritol phosphate pathway (MEP) (for reviews, see Refs. 11-13). Both pathways are compartmentalized as follows: the MVA in the cytoplasm to provide sterols, the many sesquiterpenes, and the prenyl chains of ubiquinones, and the MEP one in the plastids Tables 1 and 2

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The Arabidopsis thaliana FPS1 Gene Generates a Novel mRNA That Encodes a Mitochondrial Farnesyl-diphosphate Synthase Isoform

Cited by 158 publications

References 44 publications

Maize cDNAs Expressed in Endosperm Encode Functional Farnesyl Diphosphate Synthase with Geranylgeranyl Diphosphate Synthase Activity

Maize cDNAs Expressed in Endosperm Encode Functional Farnesyl Diphosphate Synthase with Geranylgeranyl Diphosphate Synthase Activity

The Farnesyl-diphosphate/Geranylgeranyl-diphosphate Synthase of Toxoplasma gondii Is a Bifunctional Enzyme and a Molecular Target of Bisphosphonates

Contribution of the Mevalonate and Methylerythritol Phosphate Pathways to the Biosynthesis of Dolichols in Plants

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