Disease relevance of shikimic acid

• Furthermore, we discuss the evolutionary and metabolic implications of the presence of two shikimate dehydrogenases in E. coli and other organisms [1].
• Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae [2].
• Purification and characterization of shikimate kinase enzyme activity in Bacillus subtilis [3].
• A cDNA encoding potato (Solanum tuberosum L.) 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, the first enzyme of the shikimate pathway, was cloned into phage lambda gt11 [4].
• Here we report such an operon organization in a cyanobacterium (Synechocystis PCC6803) involving the genes for four RPs that are important in the GTPase function of the ribosome and the aroC gene encoding chorismate synthase, a key enzyme in the shikimate pathway for biosynthesis of aromatic amino acids and cell wall components [5].

High impact information on shikimic acid

• Genes encoding chorismate synthase, the final shikimate pathway enzyme, were cloned from T. gondii and P. falciparum [6].
• This enzyme is a potential target for new antifungal and antibacterial drugs as the shikimate pathway is absent from mammals and DHQS is required for pathogen virulence [7].
• Downregulation of ODO1 in transgenic P. hybrida Mitchell plants strongly reduced volatile benzenoid levels through decreased synthesis of precursors from the shikimate pathway [8].
• Several of the assays, including those for sucrose phosphate synthase, ADP glucose pyrophosphorylase (AGPase), ferredoxin-dependent glutamate synthase, glycerokinase, and shikimate dehydrogenase, provide large advantages over previous approaches [9].
• Transketolase (TK) catalyzes reactions in the Calvin cycle and the oxidative pentose phosphate pathway (OPPP) and produces erythrose-4-phosphate, which is a precursor for the shikimate pathway leading to phenylpropanoid metabolism [10].

Chemical compound and disease context of shikimic acid

• The Escherichia coli aroF and aroG genes encode the tyrosine-sensitive and the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthases, respectively, two of the three isoenzymes that control carbon flow through the shikimate pathway [11].
• Type I dehydroquinase from the shikimate pathway of Escherichia coli dehydrates dehydroquinate to dehydroshikimate. pH/log Vmax profiles of the enzyme indicate the presence of a single ionizing group with a pKa of 6 [12].
• The 28.0 g/L of shikimic acid synthesized in 14% yield by E. coli SP1.1/pKD12.138 in 48 h as a 1.6:1.0:0.65 (mol/mol/mol) shikimate/quinate/dehydroshikimate mixture is typical of synthesized product mixtures [13].
• By apparently repressing shikimate transport, the aforementioned E. coli SP1.1/pKD12.138 synthesized 52 g/L of shikimic acid in 18% yield from glucose as a 14:1.0:3.0 shikimate/quinate/dehydroshikimate mixture [13].
• Crystallographic analysis of EPSP synthase from Escherichia coli, in complex with shikimate/glyphosate at 1.5 Angstroms resolution, revealed that binding of shikimate induces changes around the backbone of the active site, which in turn impact the efficient binding of glyphosate [14].

Biological context of shikimic acid

• Glyphosate-based herbicides, such as Roundup, target the shikimate pathway enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, the functionality of which is absolutely required for the survival of plants [15].
• Hence, they integrate plastidial pathways, such as photosynthesis, starch biosynthesis, the oxidative pentose phosphate pathway and the shikimate pathway, into the metabolic network of plant cells [16].
• We report the dramatic changes which occur to the shikimate pathway enzyme dehydroquinase when ligand is attached to its active site after borohydride reduction of the mechanistically important Schiff's base intermediates [17].
• This is the first study that describes the crystal structure as well as mutagenesis and mechanistic analysis of this new class of shikimate dehydrogenase [2].
• These results present the first biochemical/molecular genetic evidence of shikimate pathway in the cyanobacterial group [5].

Anatomical context of shikimic acid

• MurA catalyzes the first step in the biosynthesis of the bacterial cell wall; AroA is the sixth enzyme of the shikimate pathway leading to the synthesis of aromatic compounds in numerous microorganisms and plants [18].
• Activities of five other shikimate pathway enzymes were, however, similar in the adapted and nonadapted cells, and the concentrations of the free aromatic amino acids in the two cell lines were also similar [19].
• A functional AtPPT1 providing plastids with PEP for the shikimate pathway is therefore essential for correct leaf development [20].
• B6C3HF1 mouse vibrissae follicles were cultured in serum-free medium for 7 days at 31 degrees C. Follicles treated with water-soluble (WS) extracts of the leaves, fruits and roots of Illicium anisatum or shikimic acid grew significantly longer than controls [21].
• This suggests that chorismate, a metabolite of the shikimate pathway, is present not only in the plastids but also in the cytosol of plant cells [22].

Associations of shikimic acid with other chemical compounds

• We show that p-coumaroyl-CoA and caffeoyl-CoA are the best acyl group donors and that the acyl group is transferred more efficiently to shikimate than to quinate [23].
• For example, feedback-regulated enzymes of the shikimate pathway are anthranilate synthase on the branch leading to Trp and chorismate mutase on the branch leading to Phe and Tyr [24].
• In Neurospora, five structural and two regulatory genes mediate the initial events in quinate/shikimate metabolism as a carbon source [25].
• Phenylalanine uptake into the root, its root-to-shoot translocation, and Phe and phenylpropanoid contents were unaltered in pig1-1, indicating that pig1-1 is not affected in amino acid translocation or the shikimate pathway [24].
• There was also an increase in shikimate as a precursor of secondary plant products and marked changes in the levels of the minor sugars involved in ascorbate synthesis and cell wall metabolism [26].

Gene context of shikimic acid

• Sorbate hypersensitivity was detected in mutants of the shikimate biosynthesis pathway, strains lacking the PDR12 efflux pump or WAR1, a transcription factor mediating stress induction of PDR12 [27].
• This 16 kDa open reading frame has been identified as aroK, the gene for shikimic acid kinase I. Thus the dam gene is part of an operon containing aroK, aroB, urf74.3, and dam [28].
• Cloning and analysis of the shiA gene, which encodes the shikimate transport system of escherichia coli K-12 [29].
• The auxotrophic requirements of a strain mutant for both urf1 and aroL (encoding shikimate kinase II) are consistent with shikimate kinase deficiency [30].
• 5-enolpyruvylshikimate-3-phosphate synthase (EPSPs), the target of the herbicide glyphosate, catalyzes an essential step in the shikimate pathway common to aromatic amino acid biosynthesis [31].

Analytical, diagnostic and therapeutic context of shikimic acid

• We have identified the interaction of EPSP synthase with one of its two substrates (shikimate 3-phosphate) and with the widely used herbicide glyphosate by x-ray crystallography [32].
• Primary sequence analyses of BzdR showed an unusual modular organization with an N-terminal region homologous to members of the HTH-XRE family of transcriptional regulators and a C-terminal region similar to shikimate kinases [33].
• The transition from reserve accumulation to seed desiccation was associated with a major metabolic switch, resulting in the accumulation of distinct sugars, organic acids, nitrogen-rich amino acids, and shikimate-derived metabolites [34].
• The results of Northern and Southern blot analyses are consistent with the existence of only one shikimate kinase gene per haploid genome in tomato [35].
• The shikimate pathway presents an attractive target for malaria chemotherapy [36].

References