The natural product rapamycin, produced during fermentation by Streptomyces hygroscopicus, is known for its potent antifungal, immunosuppressive, and anticancer activities. During rapamycin biosynthesis, the amino acid l-pipecolate is incorporated into the rapamycin molecule. We investigated the use of precursor-directed biosynthesis to create new rapamycin analogs by substitution of unusual l-pipecolate ...

The YycFG two-component system, originally identified in Bacillus subtilis, is highly conserved among gram-positive bacteria with low G+C contents. In Streptococcus pneumoniae, the YycF response regulator has been reported to be essential for cell growth, but the signal to which it responds and the gene members of the regulon remain ...

Mannosamine (2-deoxy-2-amino-D-mannose) is unable to block GPI biosynthesis in Plasmodium falciparum: neither parasite development nor GPI biosynthesis were blocked by mannosamine treatment in P. falciparum cultures. Further, it was shown by metabolic labeling with [3H]mannosamine and subsequent monosaccharide analysis by high pH anion exchange chromatography that mannosamine is converted at ...

Medium-length methylketones (C7-C15) are highly effective in protecting plants from numerous pests. We used a biochemical genomics approach to elucidate the pathway leading to synthesis of methylketones in the glandular trichomes of the wild tomato Lycopersicon hirsutum f glabratum (accession PI126449). A comparison of gland EST databases from accession PI126449 ...

Mammalian arginases I and II require an intact binuclear manganese cluster for the hydrolysis of L-arginine to generate L-ornithine and urea. Although arginase isozymes differ in terms of their tissue distribution, cellular localization, and metabolic function, each employs a metal-activated hydroxide mechanism for catalysis. To date, the best arginase inhibitors ...

The role and metabolism of indole-3-acetic acid in gram-negative bacteria is well documented, but little is known about indole-3-acetic acid biosynthesis and regulation in gram-positive bacteria. The phytopathogen Rhodococcus fascians, a gram-positive organism, incites diverse developmental alterations, such as leafy galls, on a wide range of plants. Phenotypic analysis of ...

Isoprenoid biosynthesis via the methylerythritol phosphate pathway is a target against pathogenic bacteria and the malaria parasite Plasmodium falciparum. 4-(Hydroxyamino)-4-oxobutylphosphonic acid and 4-[hydroxy(methyl)amino]-4-oxobutyl phosphonic acid, two novel inhibitors of DXR (1-deoxy-D-xylulose 5-phosphate reducto-isomerase), the second enzyme of the pathway, have been synthesized and compared with fosmidomycin, the best known inhibitor ...

The biosynthesis of the monoterpenes terpinolene and myrcene and the sesquiterpene beta-caryophyllene in roots and leaves of two carrot varieties (Daucus carota L. cultivars Bolero and Kazan) were investigated by in vivo feeding experiments with [5,5-2H2]-mevalonic acid lactone (d2-MVL) and [5,5-2H2]-1-deoxy-D-xylulose (d2-DOX). The volatiles of the tissues were extracted by ...

Incubations of [8(R)-2H]9(S)-hydroperoxy-10(E),12(Z)-octadecadienoic acid, [14(R)-2H]13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid and [14(S)-2H]13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid were performed with preparations of plant tissues containing divinyl ether synthases. In agreement with previous studies, generation of colneleic acid from the 8(R)-deuterated 9(S)-hydroperoxide was accompanied by loss of most of the deuterium label (retention, 8%), however, the opposite result (98% ...

The wound-activated biosynthesis of phytoalexin hydroxycinnamic acid amides of tyramine was compared in untransformed and transgenic tobacco (Nicotiana tabacum) lines that express tryptophan decarboxylase (TDC), tyrosine decarboxylase (TYDC), or both activities. Transgenic in vitro-grown tobacco lines expressing TDC activity accumulated high levels of tryptamine but not hydroxycinnamic amides of tryptamine. ...

Appressorium formation is believed to be an important event in establishing a successful interaction between the late blight pathogen, Phytophthora infestans, and its host plants potato and tomato. An understanding of molecular events occurring in appressorium development could suggest new strategies for controlling late blight. We used parallel studies of ...

BACKGROUND: There are several reports in the literature indicating that fusidic acid owns functions similar to those of cyclosporin. As cyclosporin has effectively been used in frequently relapsing steroid-responsive nephrotic syndrome we carried out this study to determine whether fusidic acid used along with prednisolone diminishes rate of steroid-responsive nephrotic ...

Peptaibols and the related peptaibiotics are linear, amphipathic polypeptides. More than 300 of these secondary metabolites have been described to date. These compounds are composed of 5-20 amino acids and are generally produced in microheterogeneous mixtures. Peptaibols and peptaibiotics with unusual amino acid content are the result of non-ribosomal biosynthesis. ...

Malaria, a tropical disease caused by Plasmodium sp., has been haunting mankind for ages. Unsuccessful attempts to develop a vaccine, the emergence of resistance against the existing drugs and the increasing mortality rate all call for immediate strategies to treat it. Intense attempts are underway to develop potent analogues of ...

Among shigellas isolated from patients in England and Wales in 2002, 10% of subgroups A, B and C, and 13% of subgroup D (Shigella sonnei), were resistant to nalidixic acid. As a consequence, should antimicrobial therapy be indicated, the efficacy of nalidixic acid as the preferred treatment for children with ...

Plastids are the organelles of plants and algae that house photosynthesis and many other biochemical pathways. Plastids contain a small genome, but most of their proteins are encoded in the nucleus and posttranslationally targeted to the organelle. When plants and algae lose photosynthesis, they virtually always retain a highly reduced ...

The biosynthesis of fukinolic acid, which had been isolated from the Japanese fuki vegetable, Petasites japonicus, was investigated by feeding selected (13)C-labeled compounds to axenic cultures of P. japonicus. [1,2-(13)C(2)] sodium acetate and [1-(13)C] L-tyrosine were incorporated into the fukiic acid sub group, while [3-(13)C] L-phenylalanine was incorporated into the ...

Metabolic pathways sequestered within the leucoplast of developing oilseeds ensure a balanced supply of substrates and cofactors for fatty acid biosynthesis. NADP-dependent malic enzyme (NADP-ME) may be important in supplying both carbon and NADPH for fatty acid biosynthesis in the developing endosperm of the oilseed Ricinus communis. NADP-ME was purified ...

OBJECTIVE: This retrospective study was designed to investigate the possible reasons for an apparent increase in fusidic acid resistance among Staphylococcus aureus. Materials and methods: The Datastore records of the Communicable Disease Surveillance Centre, Wales, UK were reviewed in conjunction with information concerning the prescribing of fusidic acid. RESULTS: During ...

Development of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized in P. falciparum. These facts prompted us to evaluate various terpenes, ...

9-cis-Epoxycarotenoid dioxygenase (NCED), a key enzyme in abscisic acid (ABA) biosynthesis, cleaves the olefinic double bond of 9-cis-epoxycarotenoid. Several analogues of nordihydroguaiaretic acid (NDGA) were designed and synthesized, and their efficacy as inhibitors of NCED was examined. One of the synthesized compounds (20) was found to be an inhibitor of ...

Although a pathway for betacyanin biosynthesis has been postulated, most of the catalytic steps have not yet been identified or demonstrated with biochemical evidence. In the postulated pathway, the glucose moiety of betanin is conjugated to the aglycone, betanidin, because the glucosyltransferase (GT) activity that produces betanin has been reported ...

Amino acid biosynthesis and central carbon metabolism of Pichia pastoris were studied using biosynthetically directed fractional (13)C labeling. Cells were grown aerobically in a chemostat culture fed at two dilution rates (0.05 h(-1), 0.16 h(-1)) with glycerol as the sole carbon source. For investigation of amino acid biosynthesis and comparison ...

Lipids in the sex pheromone gland of females of the Z-strain of Ostrinia nubilalis were analyzed for fatty acyl pheromone analogs (FAPAs) and other potential biosynthetic intermediates. More than 80% of the FAPAs were found in the triacylglycerols (TGs), with smaller amounts found in the phosphatidyl cholines, ethanolamines, and serines. ...

OBJECTIVE: To determine the presence of fluoroquinolone resistance in Typhoidal salmonellae at Rawalpindi and the role of nalidixic acid in predicting the resistance against fluoroquinolones in Microbiology Laboratory, Department of Pathology, Army Medical College, Rawalpindi. METHODS: One hundred consecutive clinical isolates of Typhoidal salmonellae isolated from blood culture samples were ...

Polyenes constitute a large class of natural metabolites produced by giant multifunctional enzymes in a process resembling fatty acid biosynthesis. Like fatty acids, polyene macrolides and other polyketides are assembled by decarboxylative condensations of simple carboxylic acids. But while fatty acid intermediates are fully reduced, polyene macrolide intermediates suffer the ...

OBJECTIVES AND METHODS: To describe cases of fusidic acid-associated sideroblastic anaemia from the French Pharmacovigilance database. RESULTS: Six cases of sideroblastic anaemia associated with oral fusidic acid treatment were retrieved. Four females and two males (mean age 65.3 yr) developed severe anaemia (mean haemoglobin level: 6.9 g/dL) within 32-190 d ...

Bacterial enoyl-acyl carrier protein reductase (ENR) catalyzes an essential step in fatty acid biosynthesis. ENR is an attractive target for narrow-spectrum antibacterial drug discovery because of its essential role in metabolism and its sequence conservation across many bacterial species. In addition, the bacterial ENR sequence and structural organization are distinctly ...

Lotus japonicus was shown to contain the two nitrile glucosides rhodiocyanoside A and rhodiocyanoside D as well as the cyanogenic glucosides linamarin and lotaustralin. The content of cyanogenic and nitrile glucosides in L. japonicus depends on plant developmental stage and tissue. The cyanide potential is highest in young seedlings and ...

The allene oxide cyclase (AOC), an enzyme in jasmonate biosynthesis, occurs in vascular bundles and ovules of tomato flowers which exhibit a tissue-specific oxylipin signature (Plant J. 24, 113-126, 2000). Constitutive overexpression of the AOC did not led to altered levels of jasmonates in leaves, but these levels increased upon ...

The steps involved in kaurenolide and fujenoic acids biosynthesis, from ent-kauradienoic acid and ent-6alpha,7alpha-dihydroxykaurenoic acid, respectively, are demonstrated in the gibberellin (GA)-deficient Gibberella fujikuroi mutant SG139, which lacks the entire GA-biosynthesis gene cluster, complemented with the P450-1 gene of GA biosynthesis (SG139-P450-1). ent-[2H]Kauradienoic acid was efficiently converted into 7beta-hydroxy[2H]kaurenolide and ...

Resistance to fusidic acid among community methicillin susceptible Staphylococcus aureus (MSSA) isolates in the United Kingdom and prescriptions for fusidic acid have both doubled over the past 6 years. A retrospective case-control study was undertaken to test the hypothesis that the use of topical fusidic acid is associated with the ...

Accumulation of proline has been observed in a large number of plant species in response to drought and salt stresses, suggesting a key role of this amino acid in plant stress adaptation. Upstream components of the proline biosynthesis signal transduction pathways are still poorly defined. We provide experimental evidence that ...

An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs). Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ...

Phenazines produced by members of several bacterial genera are biologically active metabolites that function in microbial competitiveness, the suppression of soil-borne plant diseases and virulence in infectious disease. Despite recent progress towards understanding the biochemistry of phenazine synthesis, the key reactions leading to the formation of the heterocyclic scaffold common ...

Western white pine (Pinus monticola) seeds exhibit deep dormancy at maturity and seed populations require several months of moist chilling to reach their uppermost germination capacities. Abscisic acid (ABA) and its metabolites, phaseic acid (PA), dihydrophaseic acid (DPA), 7'-hydroxy ABA (7'OH ABA) and ABA-glucose ester (ABA-GE), were quantified in western ...

UDP-N-acetylmuramic acid (UDP-MurNAc) is a precursor for peptidoglycan biosynthesis in bacteria. A major difficulty in the study of this pathway is that UDP-MurNAc is not commercially available. We have developed an enzymatic synthesis scheme for UDP-MurNAc using two easily purified Escherichia coli polyhistidine tagged peptidoglycan biosynthesis enzymes, MurZ and MurB, ...

The pathway for the biosynthesis of cysteine and homocysteine in Methanococcus jannaschii has been examined using a gas chromatography-mass spectrometry (GC-MS) stable isotope dilution method to identify and quantitate the intermediates in the pathways. The first step in the pathway, and the one responsible for incorporation of sulfur into both ...

Sesamol is a potent inhibitor of fungal fatty acid biosynthesis. This effect is apparently due to inhibition of malic enzyme and the supply of NADPH that is required for this biosynthetic pathway. It is the ability of sesamol to reduce the synthesis of the coenzyme, NADPH, that makes it attractive ...

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 ...

Cytochrome p450(BioI)(CYP107H1) is believed to supply pimelic acid equivalents for biotin biosynthesis in Bacillus subtilis: we report here that the mechanistic pathway adopted by this multifunctional p450 for the in-chain cleavage of fatty acids is via consecutive formation of alcohol and threo-diol intermediates, with the likely absolute configuration of the ...

The concentration of abscisic acid in plants is regulated not only by biosynthesis, but also by metabolism. Abscisic acid is metabolized to phaseic acid via 8'-hydroxyabscisic acid, and phaseic acid is then converted to dihydrophaseic acid and its epimer. A quantitative analysis of these metabolites is important as well as ...

Plant growth and development are strongly dependent on sink-source interactions. In the majority of plants, sucrose (Suc) is the dominant form in which photo-assimilate is transported from source to sinks. Although the effects of Suc on photosynthetic metabolism have been intensively studied, the effect of Suc supply on metabolism in ...

Solid-phase biosynthetic reactions, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF), was used to gain insight into the biosynthesis of pectin oligomers. Sepharose supports bearing long pectic oligogalacturonides (OGAs) anchored through a disulfide-containing cleavable linker, were prepared. The OGAs (degrees of polymerization of 13 and 14) were efficiently ...

Due to broad and overlapping substrate specificities, aminotransferases remain the last uncharacterized enzymes from most amino acid biosynthetic pathways in Corynebacterium glutamicum. We report here a complete description of all aminotransferases participating in the biosynthesis of the branched-chain amino acids and phenylalanine in C. glutamicum. We used methods of profile ...

The pheromone component, frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane) is thought to be formed in Dendroctonus spp. bark beetles through the cyclization of oxygenated 6-methyl-6-hepten-2-one (6-MHO). Unlike many of the isoprenoid pheromone components of bark beetles, there is no obvious immediate host conifer precursor for 6-MHO or frontalin. To elucidate the biosynthetic pathway of ...

This mini-review describes a parent's search for evidence on the relative merits of two commonly used treatments for conjunctivitis. It was conducted in a very limited period of time with access to free databases (Pub Med, Cochrane Library) and only the abstracts of papers. Five relevant studies were identified that ...

The dimorphic fungus Candida albicans produces farnesol as a quorum-sensing molecule that regulates cellular morphology. The biosynthetic origin of farnesol has been resolved by treating these cells with zaragozic acid B, a potent inhibitor of squalene synthase in the sterol biosynthetic pathway. Treatment with zaragozic acid B leads to an ...

Fusidic acid is an active agent against a wide variety of gram-positive bacteria, and it has been increasingly used in methicillin-resistant Staphylococcus aureus infection. The major adverse effects are mild gastrointestinal discomfort and diarrhea. The hematological side effects such as granulocytopenia and thrombocytopenia have been rarely reported in western countries, ...

Root cultures of Swertia chirata (Gentianaceae) were grown with supplements of [1-13C]glucose, [U-13C6]glucose or [carboxy-13C]shikimic acid. 1,3,5,8-Tetrahydroxyxanthone was isolated and analysed by quantitative NMR analysis. The observed isotopomer distribution shows that 1,3,5,8-tetrahydroxyxanthone is biosynthesized via a polyketide-type pathway. The starter unit, 3-hydroxybenzoyl-CoA, is obtained from an early shikimate pathway intermediate. ...