The shikimate pathway.
01 Jun 1999-Vol. 50, Iss: 1, pp 473-503
TL;DR: The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds, the precursor of the aromatic amino acids and many aromatic secondary metabolites, and is the sole target for the herbicide glyphosate.
Abstract: The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.
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TL;DR: Large-scale transcriptional changes accompany insect-induced resistance, which is organized into specific temporal and spatial patterns and points to the existence of herbivore-specific trans-activating elements orchestrating the responses.
Abstract: ▪ Abstract Plants respond to herbivore attack with a bewildering array of responses, broadly categorized as direct and indirect defenses, and tolerance. Plant-herbivore interactions are played out on spatial scales that include the cellular responses, well-studied in plant-pathogen interactions, as well as responses that function at whole-plant and community levels. The plant's wound response plays a central role but is frequently altered by insect-specific elicitors, giving plants the potential to optimize their defenses. In this review, we emphasize studies that advance the molecular understanding of elicited direct and indirect defenses and include verifications with insect bioassays. Large-scale transcriptional changes accompany insect-induced resistance, which is organized into specific temporal and spatial patterns and points to the existence of herbivore-specific trans-activating elements orchestrating the responses. Such organizational elements could help elucidate the molecular control over the d...
1,423 citations
TL;DR: The pathway organization and the transcriptional/posttranscriptional regulation of the AAA biosynthetic network is summarized and the current limited knowledge of the subcellular compartmentalization and the metabolite transport involved in the plant AAA pathways is identified.
Abstract: L-tryptophan, L-phenylalanine, and L-tyrosine are aromatic amino acids (AAAs) that are used for the synthesis of proteins and that in plants also serve as precursors of numerous natural products, such as pigments, alkaloids, hormones, and cell wall components. All three AAAs are derived from the shikimate pathway, to which ≥30% of photosynthetically fixed carbon is directed in vascular plants. Because their biosynthetic pathways have been lost in animal lineages, the AAAs are essential components of the diets of humans, and the enzymes required for their synthesis have been targeted for the development of herbicides. This review highlights recent molecular identification of enzymes of the pathway and summarizes the pathway organization and the transcriptional/posttranscriptional regulation of the AAA biosynthetic network. It also identifies the current limited knowledge of the subcellular compartmentalization and the metabolite transport involved in the plant AAA pathways and discusses metabolic engineering efforts aimed at improving production of the AAA-derived plant natural products.
976 citations
Cites background from "The shikimate pathway."
...The seven enzymatic reactions of the shikimate pathway connect central carbon metabolism and the AAA network by converting phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P)—intermediates in glycolysis and the pentose phosphate pathways, respectively—to chorismate, the universal precursor for all AAAs and numerous metabolites derived from them (Figures 1 and 2) (12, 80, 81, 164)....
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TL;DR: The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism as discussed by the authors, which shares reactions with the Entner-Doudoroff pathway and the Calvin cycle and divides into an oxidative and non-oxidative branch.
Abstract: The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner-Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the 'Warburg effect' of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism.
817 citations
Additional excerpts
...…et al., 1995; Avignone Rossa et al., 2002; Butler et al., 2002; Li & Townsend, 2006; Borodina et al., 2008), alcohols (Jeppsson et al., 2002; Jeffries & Jin, 2004; Hahn-Hägerdal et al., 2007), nucleosides (Kamada et al., 2001) and amino acids (Marx et al., 1997; Herrmann & Weaver, 1999)....
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TL;DR: Molecular analysis is confirming the widespread presence of multiple genes encoding each of the enzymes of the oxidative pentose phosphate pathway, and differential expression of these isozymes may ensure that the kinetic properties of the activity that catalyses a specific reaction match the metabolic requirements of a particular tissue.
715 citations
TL;DR: This work investigated recently discovered glyphosate-resistant Amaranthus palmeri populations from Georgia, in comparison with normally sensitive populations, and revealed that EPSPS genes were present on every chromosome and, therefore, gene amplification was likely not caused by unequal chromosome crossing over.
Abstract: The herbicide glyphosate became widely used in the United States and other parts of the world after the commercialization of glyphosate-resistant crops. These crops have constitutive overexpression of a glyphosate-insensitive form of the herbicide target site gene, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Increased use of glyphosate over multiple years imposes selective genetic pressure on weed populations. We investigated recently discovered glyphosate-resistant Amaranthus palmeri populations from Georgia, in comparison with normally sensitive populations. EPSPS enzyme activity from resistant and susceptible plants was equally inhibited by glyphosate, which led us to use quantitative PCR to measure relative copy numbers of the EPSPS gene. Genomes of resistant plants contained from 5-fold to more than 160-fold more copies of the EPSPS gene than did genomes of susceptible plants. Quantitative RT-PCR on cDNA revealed that EPSPS expression was positively correlated with genomic EPSPS relative copy number. Immunoblot analyses showed that increased EPSPS protein level also correlated with EPSPS genomic copy number. EPSPS gene amplification was heritable, correlated with resistance in pseudo-F2 populations, and is proposed to be the molecular basis of glyphosate resistance. FISH revealed that EPSPS genes were present on every chromosome and, therefore, gene amplification was likely not caused by unequal chromosome crossing over. This occurrence of gene amplification as an herbicide resistance mechanism in a naturally occurring weed population is particularly significant because it could threaten the sustainable use of glyphosate-resistant crop technology.
626 citations
Cites background from "The shikimate pathway."
...19), a component of the shikimate pathway (11)....
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...Shikimate accumulates in plants when EPSPS is inhibited by glyphosate because shikimate-3-phosphate, a substrate in the reaction catalyzed byEPSPS, converts to shikimate and accumulates faster than it can be consumed in other metabolic pathways (11)....
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References
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TL;DR: The 4,639,221-base pair sequence of Escherichia coli K-12 is presented and reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident.
Abstract: The 4,639,221-base pair sequence of Escherichia coli K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.
7,723 citations
TL;DR: The broadspectrum herbicide glyphosate inhibits the enzymatic conversion of shikimic acid to anthranilic acid in a cell-free extract of Aerobacter, aerogenes 50% at 5 to 7 μM concentrations.
985 citations
TL;DR: The Shikimate Pathway as mentioned in this paper is a metabolic tree with many branches, which is a tree-structured approach for the analysis of the human metabolic pathway. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp 307-384.
Abstract: (1990). The Shikimate Pathway — A Metabolic Tree with Many Branche. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp. 307-384.
682 citations
01 Jan 1990
635 citations
TL;DR: Molecular characterization studies determined that the single genetic insert in line 40-3-2 contains only a portion of the cauliflower mosaic virus 35S promoter (P-E35S), the Petunia hybrida EPSPS chloroplast transit peptide (CTP), the CP4 EPSPS gene, and aportion of the 3' nontranslated region of the nopaline synthase gene (NOS 3') terminator.
Abstract: Glyphosate (N-phosphonomethyl-glycine) is the active ingredient in the nonselective herbicide Roundup. The sensitivity of crop plants to glyphosate has limited its in-season use as a postemergence herbicide. The extension of the use of Roundup herbicide to allow in-season application in major crops such as soybeans [Glycine max (L.) Merr.] would provide new weed control options for farmers. A glyphosate-tolerant soybean line, 40-3-2, was obtained through expression of the bacterial 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase, EPSPS) enzyme from Agrobacterium sp. strain CP4. Line 40-3-2 is highly tolerant to glyphosate, showing no visual injury after application of up to 1.68 kg acid equivalent (a.e.) ha -1 of glyphosate under field conditions. Molecular characterization studies determined that the single genetic insert in line 40-3-2 contains only a portion of the cauliflower mosaic virus 35S promoter (P-E35S), the Petunia hybrida EPSPS chloroplast transit peptide (CTP), the CP4 EPSPS gene, and a portion of the 3' nontranslated region of the nopaline synthase gene (NOS 3') terminator. Inheritance studies have shown that the transgene behaves as a single dominant gene and is stable over several generations.
618 citations