In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin.
AuthorsWiesner J, Henschker D, Hutchinson DB, Beck E, Jomaa H
JournalAntimicrob Agents Chemother
PubMed ID12183243
'Fosmidomycin acts through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, a key enzyme of the nonmevalonate pathway of isoprenoid biosynthesis. It possesses potent antimalarial activity in vitro and in murine malaria. In a recent clinical study, fosmidomycin was effective and well tolerated in the treatment of patients with acute uncomplicated Plasmodium ... More
Isolation of the dxr gene of Zymomonas mobilis and characterization of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
AuthorsGrolle S, Bringer-Meyer S, Sahm H
JournalFEMS Microbiol Lett
PubMed ID11004410
'The gene encoding the second enzyme of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway for isopentenyl diphosphate biosynthesis, 1-deoxy-D-xylulose 5-phosphate (DXP) reductoisomerase, was cloned and sequenced from Zymomonas mobilis. The deduced amino acid sequence showed the highest identity (48.2%) to the DXP reductoisomerase of Escherichia coli. Biochemical characterization of the purified DXP ... More
Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development.
AuthorsSteinbacher S, Kaiser J, Eisenreich W, Huber R, Bacher A, Rohdich F
JournalJ Biol Chem
PubMed ID12621040
'2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway. As it is present in many pathogens and plants, but not in man, this pathway has attracted considerable interest as a target for ... More
In vitro and in vivo antibacterial activity of FR-31564, a phosphonic acid antimicrobial agent.
AuthorsNeu HC, Kamimura T
JournalAntimicrob Agents Chemother
PubMed ID7271270
'The in vitro and in vivo activity of FR-31564 [sodium hydrogen 3-(N-hydroxyformamido)propylphosphate] against gram-positive and -negative aerobic and anaerobic bacteria was investigated and compared with that of fosfomycin, cephalexin, carbenicillin, and trimethoprim-sulfamethoxazole. The in vitro activity of FR-31564 was markedly enhanced when combined with glucose 6-phosphate or fructose 6-phosphate, but ... More
Synergy of ciprofloxacin with fosfomycin in vitro against Pseudomonas isolates from patients with cystic fibrosis.
AuthorsFigueredo VM, Neu HC
JournalJ Antimicrob Chemother
PubMed ID3139615
'Pseudomonas aeruginosa remains the most common respiratory pathogen causing morbidity and mortality in cystic fibrosis (CF) patients. The in-vitro activity of ciprofloxacin and fosfomycin (calcium and tromethamine salts) in combination against P. aeruginosa isolates from CF patients, all of whom had received previous courses of ciprofloxacin, was evaluated by agar ... More
Impact of ozone on monoterpene emissions and evidence for an isoprene-like antioxidant action of monoterpenes emitted by Quercus ilex leaves.
AuthorsLoreto F, Pinelli P, Manes F, Kollist H
JournalTree Physiol
PubMed ID14757575
'Quercus ilex (L.) leaves emit monoterpenes, particularly alpha-pinene, beta-pinene and sabinene. Apart from the monoterpene pools that are stored in specialized structures and have a clear defensive or attractive role, the function of monoterpenes in Q. ilex leaves is unknown. We tested whether monoterpenes have an antioxidant role, as has ... More
Biosynthesis of 2-methyl-3-buten-2-ol emitted from needles of Pinus ponderosa via the non-mevalonate DOXP/MEP pathway of isoprenoid formation.
AuthorsZeidler J, Lichtenthaler HK
JournalPlanta
PubMed ID11469599
'The volatile hemiterpene 2-methyl-3-buten-2-ol (MBO) is emitted from the needles of several pine species from the Western United States and contributes to ozone formation in the atmosphere. It is synthesised enzymatically from dimethylallyl diphosphate (DMAPP). We show here that needles of Pinus ponderosa Laws. incorporated [1-2H1]-1-deoxy-D-xylulose (d-DOX) into the emitted ... More
Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid biosynthesis.
AuthorsMueller C, Schwender J, Zeidler J, Lichtenthaler HK
JournalBiochem Soc Trans
PubMed ID11171210
'Enzymes of the 1-deoxy-D-xylulose 5-phosphate/2-C-methylerythritol 4-phosphate (DOXP/MEP) pathway are targets for new herbicides and antibacterial drugs. Until now, no inhibitors for the DOXP synthase have been known of. We show that one of the breakdown products of the herbicide clomazone affects the DOXP synthase. One inhibitor of the non-mevalonate pathway, ... More
Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives.
AuthorsBergan T
JournalChemotherapy
PubMed ID2085981
'The pharmacokinetic comparison of phosphonic acid derivatives is based upon a survey of available literature on the whole group of compounds and on our own studies on fosfomycin. All three clinically used compounds, fosfomycin, fosmidomycin, and alafosfalin, are available for both oral and parenteral administration. The highest bioavailability is observed ... More
Isoprene produced by leaves protects the photosynthetic apparatus against ozone damage, quenches ozone products, and reduces lipid peroxidation of cellular membranes.
AuthorsLoreto F, Velikova V
JournalPlant Physiol
PubMed ID11743121
'Many plants invest carbon to form isoprene. The role of isoprene in plants is unclear, but many experiments showed that isoprene may have a role in protecting plants from thermal damage. A more general antioxidant action has been recently hypothesized on the basis of the protection offered by exogenous isoprene ... More
Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa.
AuthorsAltincicek B, Hintz M, Sanderbrand S, Wiesner J, Beck E, Jomaa H
JournalFEMS Microbiol Lett
PubMed ID11034300
'Two Pseudomonas aeruginosa genes encoding the enzymes 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase, both involved in the mevalonate-independent biosynthesis of isoprenoids, have been expressed as recombinant enzymes in Escherichia coli. The purified P. aeruginosa DXP reductoisomerase was inhibited by submicromolar concentrations of the antibiotics fosmidomycin and FR-900098 in a ... More
Isoprenoid biosynthesis in Synechocystis sp. strain PCC6803 is stimulated by compounds of the pentose phosphate cycle but not by pyruvate or deoxyxylulose-5-phosphate.
AuthorsErshov YV, Gantt RR, Cunningham Jr FX, Gantt E
JournalJ Bacteriol
PubMed ID12193620
'The photosynthetic cyanobacterium Synechocystis sp. strain PCC6803 possesses homologs of known genes of the non-mevalonate 2-C-methyl-D-erythritol 2-phosphate (MEP) pathway for synthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Isoprenoid biosynthesis in extracts of this cyanobacterium, measured by incorporation of radiolabeled IPP, was not stimulated by pyruvate, an initial substrate ... More
A 23.4 kb segment at the 69 degrees-70 degrees region of the Bacillus subtilis genome.
'Within the framework of the international project aimed at the sequencing of the Bacillus subtilis genome, a 23.4 kb chromosome segment has been cloned and sequenced. This region (23 433 bp; 69 degrees-70 degrees of the genetic map) contains 17 complete ORFs and a partial one. A homology search for ... More
Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development.
AuthorsRodríguez-Concepción M, Forés O, Martinez-García JF, González V, Phillips MA, Ferrer A, Boronat A
JournalPlant Cell
PubMed ID14660801
'Plants synthesize an astonishing diversity of isoprenoids, some of which play essential roles in photosynthesis, respiration, and the regulation of growth and development. Two independent pathways for the biosynthesis of isoprenoid precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA) pathway and the plastidial methylerythritol phosphate (MEP) pathway. ... More
E. coli MEP synthase: steady-state kinetic analysis and substrate binding.
AuthorsKoppisch AT, Fox DT, Blagg BS, Poulter CD
JournalBiochemistry
PubMed ID11772021
'2-C-Methyl-D-erythritol-4-phosphate synthase (MEP synthase) catalyzes the rearrangement/reduction of 1-D-deoxyxylulose-5-phosphate (DXP) to methylerythritol-4-phosphate (MEP) as the first pathway-specific reaction in the MEP biosynthetic pathway to isoprenoids. Recombinant E. coli MEP was purified by chromatography on DE-52 and phenyl-Sepharose, and its steady-state kinetic constants were determined: k(cat) = 116 +/- 8 s(-1), ... More
Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.
AuthorsJomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E
JournalScience
PubMed ID10477522
'A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. ... More
Planting the seeds of new antimalarial drugs.
AuthorsRidley RG
JournalScience
PubMed ID10498534
Studies on new phosphonic acid antibiotics. IV. Structure determination of FR-33289, FR-31564 and FR-32863.
AuthorsKuroda Y, Okuhara M, Goto T, Okamoto M, Terano H, Kohsaka M, Aoki H, Imanaka H
JournalJ Antibiot (Tokyo)
PubMed ID7372547
The structure of novel phosphonic acid antibiotics FR-33289, FR-31564, and FR-32863, produced by strains of Streptomyces, have been established as I, II, and III, respectively, on the basis of spectroscopic and chemical evidences. ... More
Meniscal bearing dislocation in the Oxford knee.
AuthorsVerhaven E, Handelberg F, Casteleyn PP, Opdecam P
JournalActa Orthop Belg
PubMed ID1772021
The Oxford knee is a unicompartmental knee prosthesis with a polyethylene meniscal bearing. Anterior dislocation or medial subluxation has been described in lateral compartment arthroplasties. The authors present the case of a medial dislocation of the lateral meniscal bearing and a review of the literature concerning meniscal bearing instability in ... More
Studies on new phosphonic acid antibiotics. II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds.
AuthorsIguchi E, Okuhara M, Kohsaka M, Aoki H, Imanaka H
JournalJ Antibiot (Tokyo)
PubMed ID7372546
A new species of Streptomyces which produces a new cell wall-inhibitory antibiotic, FR-900098 containing phosphonic acid in its molecule, is named and described. The species name proposed, Streptomyces rubellomurinus, refers to the aerial mass color. Streptomyces rubellomurinus subsp. indigoferus also produces FR-900098 and the related compound FR-33289. FR-900098 related compounds, ... More
Studies on new phosphonic acid antibiotics. III. Isolation and characterization of FR-31564, FR-32863 and FR-33289.
AuthorsOkuhara M, Kuroda Y, Goto T, Okamoto M, Terano H, Kohsaka M, Aoki H, Imanaka H
JournalJ Antibiot (Tokyo)
PubMed ID6768705
Three phosphonic acid antibiotics were found to be produced in the fermentation broths of Streptomyces. FR-31564 and FR-32863 were produced by Streptomyces lavendulae. FR-33289 was produced by a strain of Streptomyces, identified as Streptomyces rubellomurinus subsp. indigoferus. They are distinct from, but resemble FR-900098 which was reported in our preceding ... More
Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli.
AuthorsSakamoto Y, Furukawa S, Ogihara H, Yamasaki M
JournalBiosci Biotechnol Biochem
PubMed ID14519998
Adenylate cyclase deficient (cya) mutants of E. coli K-12 were found to be resistant to fosmidomycin, a specific inhibitor of the non-mevalonate pathway, just like to fosfomycin. E. coli glpT mutants were resistant to fosfomycin and also to fosmidomycin. This fact shows that fosmidomycin was transported inside via the glycerol-3-phosphate ... More
Acyloxyalkyl ester prodrugs of FR900098 with improved in vivo anti-malarial activity.
AuthorsOrtmann R, Wiesner J, Reichenberg A, Henschker D, Beck E, Jomaa H, Schlitzer M
JournalBioorg Med Chem Lett
PubMed ID12798327
FR900098 represents an improved derivative of the new antimalarial drug fosmidomycin and acts through inhibition of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield ... More
Non-mevalonate isoprenoid biosynthesis: enzymes, genes and inhibitors.
AuthorsLichtenthaler HK
JournalBiochem Soc Trans
PubMed ID11171208
The essential steps of the novel non-mevalonate pathway of isopentenyl diphosphate and isoprenoid biosynthesis in plants are described. The first five enzymes and genes of this 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway are known. The herbicide fosmidomycin specifically blocks the second enzyme, the DOXP reductoisomerase. The DOXP/MEP pathway is also present ... More
Cloning and heterologous expression of a cDNA encoding 1-deoxy-D-xylulose-5-phosphate reductoisomerase of Arabidopsis thaliana.
AuthorsSchwender J, Müller C, Zeidler J, Lichtenthaler HK
JournalFEBS Lett
PubMed ID10428488
Various plant isoprenoids are synthesized via the non-mevalonate pathway of isopentenyl diphosphate formation. In this pathway, 1-deoxy-D-xylulose 5-phosphate (DOXP), the first intermediate, is transformed to 2-C-methyl-D-erythritol 4-phosphate (MEP) by an enzyme which was recently cloned from Escherichia coli. In order to find a plant homologue of this 1-deoxy-D-xylulose 5-phosphate reductoisomerase ... More
FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability.
AuthorsKojo H, Shigi Y, Nishida M
JournalJ Antibiot (Tokyo)
PubMed ID7378171
Mutants which acquired resistance to FR-31564 were also resistant to fosfomycin and vice versa. Some exceptions to cross-resistance were found among clinical isolates of certain species. FR-31564 was found to be incorporated into bacterial cells more efficiently than fosfomycin although the extent of incorporation varied among species. In particular, the ... More
Inhibition of bacterial isoprenoid synthesis by fosmidomycin, a phosphonic acid-containing antibiotic.
AuthorsShigi Y
JournalJ Antimicrob Chemother
PubMed ID2676937
The mechanism of action of fosmidomycin (FR-31564), a phosphonic acid containing antibiotic, was examined against Escherichia coli, Micrococcus luteus and other bacteria. It converted growing Esch. coli cells into spheroplasts or swollen cells, but did not inhibit the enzymatic reactions of cell wall synthesis in ether-treated cells. Unlike bicyclomycin, phenethyl ... More
Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis.
AuthorsOkada K, Kawaide H, Kuzuyama T, Seto H, Curtis IS, Kamiya Y
JournalPlanta
PubMed ID12029484
Transgenic plants of Arabidopsis thaliana (L.) Heynh. (ecotype Columbia) expressing the antisense AtMECT gene, encoding 2- C-methyl- D-erythritol 4-phosphate cytidylyltransferase, were generated to elucidate the physiological role of the nonmevalonate pathway for production of ent-kaurene, the latter being the plastidic precursor of gibberellins. In transformed plants pigmentation and accumulation of ... More
Isoprenoid biosynthesis. Metabolite profiling of peppermint oil gland secretory cells and application to herbicide target analysis.
AuthorsLange BM, Ketchum RE, Croteau RB
JournalPlant Physiol
PubMed ID11553758
Two independent pathways operate in plants for the synthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of all isoprenoids. The mevalonate pathway is present in the cytosol, whereas the recently discovered mevalonate-independent pathway is localized to plastids. We have used isolated peppermint (Mentha piperita) oil ... More
Comparison of the response of Escherichia coli to fosfomycin and fosmidomycin.
AuthorsKanimoto Y, Greenwood D
JournalEur J Clin Microbiol
PubMed ID3311734
The responses of Escherichia coli to fosfomycin and fosmidomycin were investigated by continuous turbidimetric monitoring of cultures exposed to the drugs and by microscopy. The activity of both agents was potentiated by glucose-6-phosphate, suggesting that they share the inducible hexose phosphate transport system in Escherichia coli, but several differences of ... More
In vitro and in vivo antibacterial activities of FR-31564, a new phosphonic acid antibiotic.
AuthorsMine Y, Kamimura T, Nonoyama S, Nishida M, Goto S, Kuwahara S
JournalJ Antibiot (Tokyo)
PubMed ID7372548
FR-31564, a new phosphonic acid antibiotic, was active against most Gram-negative bacteria except Serratia marcescens and glucose-nonfermenting Gram-negative rods excluding Pseudomonas aeruginosa. The antibacterial activity in vitro of FR-31564 was stronger than that of fosfomycin especially against Escherichia coli, Klebsiella pneumoniae, Enterobacter species and P. aeruginosa. FR-31564 also was active ... More
Biosynthetic pathway of insect juvenile hormone III in cell suspension cultures of the sedge Cyperus iria.
AuthorsBede JC, Teal PE, Goodman WG, Tobe SS
JournalPlant Physiol
PubMed ID11598232
In most insect species, juvenile hormones regulate critical physiological processes such as metamorphosis and reproduction. In insects, these sesquiterpenoids are synthesized by retrocerebral endocrine organs, the corpora allata, via the classical mevalonate (MVA) pathway. One of these compounds, juvenile hormone III (JH III), has also been identified in the sedge ... More
Inhibition of paclitaxel and baccatin III accumulation by mevinolin and fosmidomycin in suspension cultures of Taxus baccata.
AuthorsPalazón J, Cusidó RM, Bonfill M, Morales C, Piñol MT
JournalJ Biotechnol
PubMed ID12568744
To achieve a better understanding of the metabolism and accumulation of paclitaxel and baccatin III in cell cultures of Taxus, inhibitors of the early steps in the terpenoid pathway were applied to a cell suspension culture of Taxus baccata: fosmidomycin as an inhibitor of the non-mevalonate branch of the pathway, ... More
A gene cluster for the mevalonate pathway from Streptomyces sp. Strain CL190.
AuthorsTakagi M, Kuzuyama T, Takahashi S, Seto H
JournalJ Bacteriol
PubMed ID10894721
A biosynthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1. 1.1.34), the rate-limiting enzyme of the mevalonate pathway for isopentenyl diphosphate biosynthesis, had previously been purified from Streptomyces sp. strain CL190 and its corresponding gene (hmgr) had been cloned (S. Takahashi, T. Kuzuyama, and H. Seto, J. Bacteriol. 181:1256-1263, 1999). Sequence analysis ... More
The non-mevalonate isoprenoid biosynthesis of plants as a test system for new herbicides and drugs against pathogenic bacteria and the malaria parasite.
AuthorsLichtenthaler HK, Zeidler J, Schwender J, Müller C
JournalZ Naturforsch [C]
PubMed ID10928537
Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since ... More
Activity of fosmidomycin in an in vitro model of the treatment of bacterial cystitis.
AuthorsKanimoto Y, Greenwood D
JournalInfection
PubMed ID3325431
The response to fosmidomycin of four strains of Escherichia coli was studied in an in vitro model of the treatment of bacterial cystitis. Three susceptible strains of E. coli responded well to relatively low concentrations of fosmidomycin: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for ... More
Relationship between plasma catecholamine levels and electrocortical state in the mature fetal lamb.
AuthorsReid DL, Jensen A, Phernetton TM, Rankin JH
JournalJ Dev Physiol
PubMed ID2283463
In late pregnancy the electrocortical activity (ECoG) in the ovine fetus starts to cycle between high and low voltage states. During the high voltage states of this activity fetal regional blood flows are decreased, and heart rate and fetal arterial blood pressure are both increased. Jensen et al. (1986) have ... More
Cloning of a gene from Escherichia coli that confers resistance to fosmidomycin as a consequence of amplification.
AuthorsFujisaki S, Ohnuma S, Horiuchi T, Takahashi I, Tsukui S, Nishimura Y, Nishino T, Kitabatake M, Inokuchi H
JournalGene
PubMed ID8917080
A gene conferring resistance to fosmidomycin (Fs) was cloned from the gene pool of a wild-type strain of Escherichia coli. The cloned DNA fragment was sequenced and shown to encode a putative polypeptide of 406 amino acids (aa) with a molecular weight of 43303. The gene mapped at 10.9 min ... More
Methyl palmitate: a novel product of the Medfly (Ceratitis capitata) corpus allatum.
AuthorsMoshitzky P, Miloslavski I, Aizenshtat Z, Applebaum SW
JournalInsect Biochem Mol Biol
PubMed ID14599501
The corpus allatum (CA) of adult female Ceratitis capitata produces methyl palmitate (MP) in vitro, in addition to JHB(3) and JH III. Biosynthesized MP migrates on TLC and co-elutes from RP-18 HPLC with synthetic MP. Its identity is verified herein by GCMS. MP production is up-regulated twofold by mevastatin, an ... More
The Deoxyxylulose Phosphate Pathway for the Biosynthesis of Plastidic Isoprenoids: Early Days in Our Understanding of the Early Stages of Gibberellin Biosynthesis.
AuthorsSponsel VM
JournalJ Plant Growth Regul
PubMed ID11986759
The identification of a novel pathway for isopentenyl diphosphate synthesis by Rohmer, Arigoni and colleagues in the early 1990's has led to a reappraisal of terpenoid biosynthesis in many organisms. It is now apparent that in plants there are two biosynthetic routes to isopentenyl diphosphate-the classical mevalonate pathway in the ... More
Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose.
AuthorsYamazaki Y, Kitajima M, Arita M, Takayama H, Sudo H, Yamazaki M, Aimi N, Saito K
JournalPlant Physiol
PubMed ID14657405
Camptothecin derivatives are clinically used antitumor alkaloids that belong to monoterpenoid indole alkaloids. In this study, we investigated the biosynthetic pathway of camptothecin from [1-13C]glucose (Glc) by in silico and in vivo studies. The in silico study measured the incorporation of Glc into alkaloids using the Atomic Reconstruction of Metabolism ... More
1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid biosynthesis during tomato fruit ripening.
AuthorsRodríguez-Concepción M, Ahumada I, Diez-Juez E, Sauret-Güeto S, Lois LM, Gallego F, Carretero-Paulet L, Campos N, Boronat A
JournalPlant J
PubMed ID11532167
The recently discovered 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the biosynthesis of plastid isoprenoids (including carotenoids) is not fully elucidated yet despite its central importance for plant life. It is known, however, that the first reaction completely specific to the pathway is the conversion of 1-deoxy-D-xylulose 5-phosphate (DXP) into MEP by ... More
Isoprene increases thermotolerance of fosmidomycin-fed leaves.
AuthorsSharkey TD, Chen X, Yeh S
JournalPlant Physiol
PubMed ID11299379
Isoprene is synthesized and emitted in large amounts by a number of plant species, especially oak (Quercus sp.) and aspen (Populus sp.) trees. It has been suggested that isoprene improves thermotolerance by helping photosynthesis cope with high temperature. However, the evidence for the thermotolerance hypothesis is indirect and one of ... More
Fosmidomycin, a novel chemotherapeutic agent for malaria.
AuthorsLell B, Ruangweerayut R, Wiesner J, Missinou MA, Schindler A, Baranek T, Hintz M, Hutchinson D, Jomaa H, Kremsner PG
JournalAntimicrob Agents Chemother
PubMed ID12543685
In previous studies, fosmidomycin has been shown to possess activity against Plasmodium falciparum in vitro and in the mouse model. It has a novel mode of action through inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme of the nonmevalonate pathway of isoprenoid biosynthesis, which is absent in humans. In this open-label, ... More
On-line analysis of the (13)CO(2) labeling of leaf isoprene suggests multiple subcellular origins of isoprene precursors.
AuthorsKarl T, Fall R, Rosenstiel TN, Prazeller P, Larsen B, Seufert G, Lindinger W
JournalPlanta
PubMed ID12355149
Isoprene (2-methyl-1,3-butadiene) is the most abundant biogenic hydrocarbon released from vegetation, and there is continuing interest in understanding its biosynthesis from photosynthetic precursors in leaf chloroplasts. We used on-line proton-transfer-reaction mass spectrometry (PTR-MS) to observe the kinetics of (13)C-labeling of isoprene following exposure to (13)CO(2) and then the loss of ... More
Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children.
BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination ... More
Expression and molecular analysis of the Arabidopsis DXR gene encoding 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the first committed enzyme of the 2-C-methyl-D-erythritol 4-phosphate pathway.
AuthorsCarretero-Paulet L, Ahumada I, Cunillera N, Rodríguez-Concepción M, Ferrer A, Boronat A, Campos N
JournalPlant Physiol
PubMed ID12177470
1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the first committed step of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. In Arabidopsis, DXR is encoded by a single-copy gene. We have cloned a full-length cDNA corresponding to this gene. A comparative analysis of all plant DXR sequences known to date predicted an N-terminal ... More
Crosstalk between cytosolic and plastidial pathways of isoprenoid biosynthesis in Arabidopsis thaliana.
AuthorsLaule O, Fürholz A, Chang HS, Zhu T, Wang X, Heifetz PB, Gruissem W, Lange M
JournalProc Natl Acad Sci U S A
PubMed ID12748386
In plants, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of isoprenoids, is compartmentalized: the mevalonate (MVA) pathway, which is localized to the cytosol, is responsible for the synthesis of sterols, certain sesquiterpenes, and the side chain of ubiquinone; in contrast, the recently discovered ... More
Genomic Deoxyxylulose Phosphate Reductoisomerase (DXR) Mutations Conferring Resistance to the Antimalarial Drug Fosmidomycin in E. coli.
Authors
JournalACS Synth Biol
PubMed ID30462485
Critical role for isoprenoids in apicoplast biogenesis by malaria parasites.