shikimic acid

Summary

Summary: A tri-hydroxy cyclohexene carboxylic acid important in biosynthesis of so many compounds that the shikimate pathway is named after it.

Top Publications

  1. Whipp M, Camakaris H, Pittard A. Cloning and analysis of the shiA gene, which encodes the shikimate transport system of escherichia coli K-12. Gene. 1998;209:185-92 pubmed
    ..Expression of the shiA gene does not appear to be regulated by the TyrR protein, a repressor/activator that controls the expression of other genes involved with the biosynthesis or transport of the aromatic amino acids. ..
  2. McConkey G. Targeting the shikimate pathway in the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 1999;43:175-7 pubmed
    The shikimate pathway presents an attractive target for malaria chemotherapy. Three shikimic acid analogs exhibited different effects on Plasmodium falciparum growth...
  3. Gourley D, Shrive A, Polikarpov I, Krell T, Coggins J, Hawkins A, et al. The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction. Nat Struct Biol. 1999;6:521-5 pubmed publisher
    ..The availability of these two structures opens the way for the design of highly specific enzyme inhibitors with potential importance as selective therapeutic agents...
  4. Li K, Frost J. Microbial synthesis of 3-dehydroshikimic acid: a comparative analysis of D-xylose, L-arabinose, and D-glucose carbon sources. Biotechnol Prog. 1999;15:876-83 pubmed
  5. Ran N, Draths K, Frost J. Creation of a shikimate pathway variant. J Am Chem Soc. 2004;126:6856-7 pubmed
    ..coli constructs that lack phosphoenolpruvate-based DAHP synthase activity and rely on evolved KDPGal aldolase for biosynthesis of shikimate pathway intermediates and products. ..
  6. Padyana A, Burley S. Crystal structure of shikimate 5-dehydrogenase (SDH) bound to NADP: insights into function and evolution. Structure. 2003;11:1005-13 pubmed
    ..The structure provides a framework for further investigation to discover and develop novel inhibitors targeting this essential enzyme...
  7. Bresnahan G, Manthey F, Howatt K, Chakraborty M. Glyphosate applied preharvest induces shikimic acid accumulation in hard red spring wheat (Triticum aestivum). J Agric Food Chem. 2003;51:4004-7 pubmed
    ..into the foliage and translocated to metabolically active regions in the plant where it interferes with the shikimic acid pathway...
  8. Pereira J, de Oliveira J, Canduri F, Dias M, Palma M, Basso L, et al. Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid. Acta Crystallogr D Biol Crystallogr. 2004;60:2310-9 pubmed
    ..The crystal structure of shikimate kinase from Mycobacterium tuberculosis (MtSK) complexed with MgADP and shikimic acid (shikimate) has been determined at 2...
  9. Ghosh S, Chisti Y, Banerjee U. Production of shikimic acid. Biotechnol Adv. 2012;30:1425-31 pubmed publisher
    b>Shikimic acid is a key intermediate for the synthesis of the antiviral drug oseltamivir (Tamiflu®). Shikimic acid can be produced via chemical synthesis, microbial fermentation and extraction from certain plants...

More Information

Publications61

  1. Tzin V, Malitsky S, Ben Zvi M, Bedair M, Sumner L, Aharoni A, et al. Expression of a bacterial feedback-insensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase of the shikimate pathway in Arabidopsis elucidates potential metabolic bottlenecks between primary and secondary metabolism. New Phytol. 2012;194:430-9 pubmed publisher
    ..We propose that DAHPS is a key regulatory enzyme of the shikimate pathway. Moreover, our results shed light on additional potential metabolic bottlenecks bridging plant primary and secondary metabolism. ..
  2. Vivancos P, Driscoll S, Bulman C, Ying L, Emami K, Treumann A, et al. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration. Plant Physiol. 2011;157:256-68 pubmed publisher
    ..Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. ..
  3. Maeda H, Dudareva N. The shikimate pathway and aromatic amino Acid biosynthesis in plants. Annu Rev Plant Biol. 2012;63:73-105 pubmed publisher
  4. Starcevic A, Akthar S, Dunlap W, Shick J, Hranueli D, Cullum J, et al. Enzymes of the shikimic acid pathway encoded in the genome of a basal metazoan, Nematostella vectensis, have microbial origins. Proc Natl Acad Sci U S A. 2008;105:2533-7 pubmed publisher
    The shikimic acid pathway is responsible for the biosynthesis of many aromatic compounds by a broad range of organisms, including bacteria, fungi, plants, and some protozoans...
  5. Miao H, Tallarico J, Hayakawa H, Munger K, Duffner J, Koehler A, et al. Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules. J Comb Chem. 2007;9:245-53 pubmed
    An epoxide derived from (-)-shikimic acid was attached to a solid support and used to synthesize over 5000 diverse small molecules...
  6. Johansson L, Liden G. Transcriptome analysis of a shikimic acid producing strain of Escherichia coli W3110 grown under carbon- and phosphate-limited conditions. J Biotechnol. 2006;126:528-45 pubmed
    b>Shikimic acid, which is produced in the aromatic amino acid pathway in plants and microorganisms, is an industrially interesting chiral starting material for the synthesis of many chemical substances, e.g. the influenza medicine Tamiflu...
  7. Vogan E. Shikimate dehydrogenase structure reveals novel fold. Structure. 2003;11:902-3 pubmed
  8. Coggins J, Abell C, Evans L, Frederickson M, Robinson D, Roszak A, et al. Experiences with the shikimate-pathway enzymes as targets for rational drug design. Biochem Soc Trans. 2003;31:548-52 pubmed
    ..Recent work on the third enzyme of the pathway, dehydroquinase, which occurs in two structurally and mechanistically distinct forms, is used to illustrate the present state of studies into rational drug design. ..
  9. Li K, Mikola M, Draths K, Worden R, Frost J. Fed-batch fermentor synthesis of 3-dehydroshikimic acid using recombinant Escherichia coli. Biotechnol Bioeng. 1999;64:61-73 pubmed
    ..The pronounced impact of transketolase overexpression, which increases E4P availability, on DHS titers and yields indicates that PEP availability is not a limiting factor under the fed-batch fermentor conditions employed. ..
  10. Light S, Minasov G, Shuvalova L, Duban M, Caffrey M, Anderson W, et al. Insights into the mechanism of type I dehydroquinate dehydratases from structures of reaction intermediates. J Biol Chem. 2011;286:3531-9 pubmed publisher
    ..The structures and mechanistic insight presented here may inform the design of type I DHQD enzyme inhibitors...
  11. Ducati R, Basso L, Santos D. Mycobacterial shikimate pathway enzymes as targets for drug design. Curr Drug Targets. 2007;8:423-35 pubmed
    ..In this review we describe studies on shikimate pathway enzymes, including enzyme kinetics and structural data. We have focused on mycobacterial shikimate pathway enzymes as potential targets for the development of new anti-TB agents. ..
  12. Light S, Anderson W, Lavie A. Reassessing the type I dehydroquinate dehydratase catalytic triad: kinetic and structural studies of Glu86 mutants. Protein Sci. 2013;22:418-24 pubmed publisher
    ..In addition, a complex with the reaction product reveals a novel, likely nonproductive, binding mode that suggests a mechanism of competitive product inhibition and a potential strategy for the design of therapeutics...
  13. Oliveira J, Pinto C, Basso L, Santos D. Cloning and overexpression in soluble form of functional shikimate kinase and 5-enolpyruvylshikimate 3-phosphate synthase enzymes from Mycobacterium tuberculosis. Protein Expr Purif. 2001;22:430-5 pubmed
    ..Enzyme activity measurements using coupled assays demonstrated that there was a 328-fold increase in specific activity for shikimate kinase and 101-fold increase for EPSP synthase. ..
  14. Whipp M, Pittard A. A reassessment of the relationship between aroK- and aroL-encoded shikimate kinase enzymes of Escherichia coli. J Bacteriol. 1995;177:1627-9 pubmed
    ..The corrected sequence alters the length of the aroK coding region such that the AroK and AroL proteins are now of comparable length and the homology between them extends the entire length of the two enzymes. ..
  15. McConkey G, Pinney J, Westhead D, Plueckhahn K, Fitzpatrick T, Macheroux P, et al. Annotating the Plasmodium genome and the enigma of the shikimate pathway. Trends Parasitol. 2004;20:60-5 pubmed
    ..This review uses the example of the shikimate pathway to examine the application of bioinformatics to lead experimental design in post-genomic biology. ..
  16. Knaggs A. The biosynthesis of shikimate metabolites. Nat Prod Rep. 2003;20:119-36 pubmed
    ..These include pyrrolnitrin. violacein. indole-3-acetic acid, coumarins, lignans, lignin, tannins, melanin, flavanoids, ubiquinone, TOPA quinone, PQQ, and tropanes. ..
  17. Dhaliwal B, Nichols C, Ren J, Lockyer M, Charles I, Hawkins A, et al. Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. FEBS Lett. 2004;574:49-54 pubmed
    ..Detailed knowledge of shikimate binding is an important step in the design of inhibitors of SK, which have potential as novel anti-tuberculosis agents. ..
  18. Woodard R. Unique biosynthesis of dehydroquinic acid?. Bioorg Chem. 2004;32:309-15 pubmed
    ..and Methanococcus jannaschii for the first seven enzymes (aroG, B, D, E, K, A, and C ) involved in the shikimic acid biosynthetic pathway reveal two key enzymes are missing...
  19. Johansson L, Lindskog A, Silfversparre G, Cimander C, Nielsen K, Liden G. Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate-limited and carbon-limited conditions. Biotechnol Bioeng. 2005;92:541-52 pubmed
    b>Shikimic acid is one of several industrially interesting chiral starting materials formed in the aromatic amino acid pathway of plants and microorganisms...
  20. Gan J, Gu Y, Li Y, Yan H, Ji X. Crystal structure of Mycobacterium tuberculosis shikimate kinase in complex with shikimic acid and an ATP analogue. Biochemistry. 2006;45:8539-45 pubmed
    ..SK catalyzes the reaction of phosphoryl transfer from ATP to shikimic acid (SA)...
  21. Richards T, Dacks J, Campbell S, Blanchard J, Foster P, McLeod R, et al. Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements. Eukaryot Cell. 2006;5:1517-31 pubmed
    ..Our analyses also pinpoints a minimum of 50 gene/domain loss events, demonstrating that loss and replacement events have been an important process in eukaryote genome evolution. ..
  22. Chandran S, Yi J, Draths K, von Daeniken R, Weber W, Frost J. Phosphoenolpyruvate availability and the biosynthesis of shikimic acid. Biotechnol Prog. 2003;19:808-14 pubmed
    The impact of increased availability of phosphoenolpyruvate during shikimic acid biosynthesis has been examined in Escherichia coli K-12 constructs carrying plasmid-localized aroF(FBR) and tktA inserts encoding, respectively, feedback-..
  23. Tripathi P, Rawat G, Yadav S, Saxena R. Fermentative production of shikimic acid: a paradigm shift of production concept from plant route to microbial route. Bioprocess Biosyst Eng. 2013;36:1665-73 pubmed publisher
    Different physiological and nutritional parameters affect the fermentative production of shikimic acid. In our study, Citrobacter freundii initially produced 0.62 g/L of shikimic acid in 72 h...
  24. Knop D, Draths K, Chandran S, Barker J, von Daeniken R, Weber W, et al. Hydroaromatic equilibration during biosynthesis of shikimic acid. J Am Chem Soc. 2001;123:10173-82 pubmed
    The expense and limited availability of shikimic acid isolated from plants has impeded utilization of this hydroaromatic as a synthetic starting material...
  25. Hartmann M, Bourenkov G, Oberschall A, Strizhov N, Bartunik H. Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis. J Mol Biol. 2006;364:411-23 pubmed
    ..The random sequential binding of shikimate and nucleotides is associated with domain movements. We identified a synergic mechanism by which binding of the first substrate may enhance the affinity for the second substrate. ..
  26. Srinivas R, Karmali P, Pramanik D, Garu A, Mahidhar Y, Majeti B, et al. Cationic amphiphile with shikimic acid headgroup shows more systemic promise than its mannosyl analogue as DNA vaccine carrier in dendritic cell based genetic immunization. J Med Chem. 2010;53:1387-91 pubmed publisher
    ..Here we show that cationic amphiphiles containing mannose-mimicking quinic acid and shikimic acid headgroups deliver genes to APCs via mannose receptor...
  27. Chen K, Dou J, Tang S, Yang Y, Wang H, Fang H, et al. Deletion of the aroK gene is essential for high shikimic acid accumulation through the shikimate pathway in E. coli. Bioresour Technol. 2012;119:141-7 pubmed publisher
    b>Shikimic acid (SA) is an important metabolic intermediate with diverse commercial applications...
  28. Ahn J, Lee H, Saha R, Park M, Jung J, Lee D. Exploring the effects of carbon sources on the metabolic capacity for shikimic acid production in Escherichia coli using in silico metabolic predictions. J Microbiol Biotechnol. 2008;18:1773-84 pubmed
    Effects of various industrially important carbon sources (glucose, sucrose, xylose, gluconate, and glycerol) on shikimic acid (SA) biosynthesis in Escherichia coli were investigated to gain new insight into the metabolic capability for ..
  29. Becerra Moreno A, Benavides J, Cisneros Zevallos L, Jacobo Velázquez D. Plants as biofactories: glyphosate-induced production of shikimic acid and phenolic antioxidants in wounded carrot tissue. J Agric Food Chem. 2012;60:11378-86 pubmed publisher
    ..The present project evaluated the feasibility of producing shikimic acid (SA) and phenolic compounds (PC) in wounded carrots ( Daucus carota ) treated with glyphosate...
  30. Ding L, Hofius D, Hajirezaei M, Fernie A, B rnke F, Sonnewald U. Functional analysis of the essential bifunctional tobacco enzyme 3-dehydroquinate dehydratase/shikimate dehydrogenase in transgenic tobacco plants. J Exp Bot. 2007;58:2053-67 pubmed publisher
    ..These data are discussed in the context of current models of plant intermediary metabolism...
  31. Cheng W, Chang Y, Wang W. Structural basis for shikimate-binding specificity of Helicobacter pylori shikimate kinase. J Bacteriol. 2005;187:8156-63 pubmed publisher
    Shikimate kinase (EC 2.7.1.71) catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP...
  32. Krämer M, Bongaerts J, Bovenberg R, Kremer S, Müller U, Orf S, et al. Metabolic engineering for microbial production of shikimic acid. Metab Eng. 2003;5:277-83 pubmed
    b>Shikimic acid is a high valued compound used as a key starting material for the synthesis of the neuramidase inhibitor GS4104, which was developed under the name Tamiflu for treatment of antiviral infections...
  33. Yi J, Draths K, Li K, Frost J. Altered glucose transport and shikimate pathway product yields in E. coli. Biotechnol Prog. 2003;19:1450-9 pubmed
    ..coli constructs derived from the same progenitor strain is used to compare strategies for increasing phosphoenolpyruvate availability. Constructs are cultured under the same set of fermentor-controlled conditions. ..
  34. Xing J, You C, Dong K, Sun J, You H, Dong Y, et al. Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats. Int Immunopharmacol. 2013;15:524-31 pubmed publisher
    The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats...
  35. Ye S, von Delft F, Brooun A, Knuth M, Swanson R, McRee D. The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode. J Bacteriol. 2003;185:4144-51 pubmed
    ..The flexibility of the nicotinamide mononucleotide portion of NADPH may be necessary for the substrate 3-dehydroshikimate to enter the pocket and for the release of the product shikimate...
  36. D Alessandro M, Held M, Triponez Y, Turlings T. The role of indole and other shikimic acid derived maize volatiles in the attraction of two parasitic wasps. J Chem Ecol. 2006;32:2733-48 pubmed
    ..Here, we studied the importance of shikimic acid derived VOCs for the attraction of females of the parasitoids Cotesia marginiventris and Microplitis ..
  37. Roberts C, Roberts F, Lyons R, Kirisits M, Mui E, Finnerty J, et al. The shikimate pathway and its branches in apicomplexan parasites. J Infect Dis. 2002;185 Suppl 1:S25-36 pubmed
    ..Such inhibitors may function as broad-spectrum antimicrobial agents that are effective against bacterial and fungal pathogens and apicomplexan parasites. ..
  38. Hoffmann L, Maury S, Martz F, Geoffroy P, Legrand M. Purification, cloning, and properties of an acyltransferase controlling shikimate and quinate ester intermediates in phenylpropanoid metabolism. J Biol Chem. 2003;278:95-103 pubmed publisher
    ..Thus, hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyltransferase appears to control the biosynthesis and turnover of major plant phenolic compounds such as lignin and chlorogenic acid...
  39. Singh S, Christendat D. Structure of Arabidopsis dehydroquinate dehydratase-shikimate dehydrogenase and implications for metabolic channeling in the shikimate pathway. Biochemistry. 2006;45:7787-96 pubmed
    ..The arrangement of the two functional domains reveals that the control of metabolic flux through the shikimate pathway is achieved by increasing the effective concentration of dehydroshikimate through the proximity of the two sites. ..
  40. Verdonk J, Haring M, van Tunen A, Schuurink R. ODORANT1 regulates fragrance biosynthesis in petunia flowers. Plant Cell. 2005;17:1612-24 pubmed
    ..Our studies identify ODO1 as a key regulator of floral scent biosynthesis. ..
  41. Maeda H, Shasany A, Schnepp J, Orlova I, Taguchi G, Cooper B, et al. RNAi suppression of Arogenate Dehydratase1 reveals that phenylalanine is synthesized predominantly via the arogenate pathway in petunia petals. Plant Cell. 2010;22:832-49 pubmed publisher
    ..Stable isotope labeling experiments showed that ADT1 suppression led to downregulation of carbon flux toward shikimic acid. However, an exogenous supply of shikimate bypassed this negative regulation and resulted in elevated ..
  42. Escalante A, Calderón R, Valdivia A, de Anda R, Hernandez G, Ramírez O, et al. Metabolic engineering for the production of shikimic acid in an evolved Escherichia coli strain lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system. Microb Cell Fact. 2010;9:21 pubmed publisher
    b>Shikimic acid (SA) is utilized in the synthesis of oseltamivir-phosphate, an anti-influenza drug...
  43. Hanik N, Gomez S, Best M, Schueller M, Orians C, Ferrieri R. Partitioning of new carbon as ¹¹C in Nicotiana tabacum reveals insight into methyl jasmonate induced changes in metabolism. J Chem Ecol. 2010;36:1058-67 pubmed publisher
    ..Levels were unchanged 4 h after MeJA treatment relative to controls, but were increased 2-fold by 15 h, indicating a lag in response of secondary metabolism. ..
  44. Reichau S, Jiao W, Walker S, Hutton R, Baker E, Parker E. Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: combining mechanism- and modeling-based design. J Biol Chem. 2011;286:16197-207 pubmed publisher
  45. Geng H, Liu H, Liu J, Wang C, Wen J. Insights into the metabolic mechanism of rapamycin overproduction in the shikimate-resistant Streptomyces hygroscopicus strain UV-II using comparative metabolomics. World J Microbiol Biotechnol. 2017;33:101 pubmed publisher
    ..hygroscopicus ATCC29253 (95.5 mg/L). Under optimal conditions, with the addition of 2 g/L shikimic acid, the strain's rapamycin production was further increased by approximately 34.9%, to 412.6 mg/L...
  46. Sander M, Petersen M. Distinct substrate specificities and unusual substrate flexibilities of two hydroxycinnamoyltransferases, rosmarinic acid synthase and hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl-transferase, from Coleus blumei Benth. Planta. 2011;233:1157-71 pubmed publisher
  47. Nie L, Shi X, Ko K, Lu W. A short and practical synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid. J Org Chem. 2009;74:3970-3 pubmed publisher
    Oseltamivir phosphate (1) was synthesized from (-)-shikimic acid through a short and practical synthetic route via eight steps in 47% overall yield...
  48. Pfleger B, Kim Y, Nusca T, Maltseva N, Lee J, Rath C, et al. Structural and functional analysis of AsbF: origin of the stealth 3,4-dihydroxybenzoic acid subunit for petrobactin biosynthesis. Proc Natl Acad Sci U S A. 2008;105:17133-8 pubmed publisher
    ..anthracis, also rely on production of the unique 3,4-DHBA metabolite to achieve full viability in the environment or virulence within the host. ..
  49. McDowell L, Poliks B, Studelska D, O Connor R, Beusen D, Schaefer J. Rotational-echo double-resonance NMR-restrained model of the ternary complex of 5-enolpyruvylshikimate-3-phosphate synthase. J Biomol NMR. 2004;28:11-29 pubmed
    ..We applied the REDOR restraints to the 1G6S coordinates and created a REDOR-refined xray structure that agrees with the NMR results. ..
  50. Brown K, Carpenter E, Watson K, Coggins J, Hawkins A, Koch M, et al. Twists and turns: a tale of two shikimate-pathway enzymes. Biochem Soc Trans. 2003;31:543-7 pubmed
    ..The combination of X-ray crystallography, SAXS and computational techniques provides an enhanced analysis of structural features important for the function of these complex enzymes. ..
  51. Macheroux P, Bornemann S, Ghisla S, Thorneley R. Studies with flavin analogs provide evidence that a protonated reduced FMN is the substrate-induced transient intermediate in the reaction of Escherichia coli chorismate synthase. J Biol Chem. 1996;271:25850-8 pubmed
    ..These results and their implications for the nature and kinetic properties of an observed flavin intermediate are discussed in the context of a possible role of reduced flavin as an electron donor to bound EPSP. ..
  52. Armesto N, Ferrero M, Fernandez S, Gotor V. Regioselective enzymatic acylation of methyl shikimate. Influence of acyl chain length and solvent polarity on enzyme specificity. J Org Chem. 2002;67:4978-81 pubmed
    ..The selectivity of CAL-A is almost complete with acyl donors that possess short chains. However, when acyl donors have longer chains, better results are obtained by C. antarctica lipase B (CAL-B). ..