Shikimate Pathway and Aromatic Amino Acid Biosynthesis


The shikimate pathway consists of seven enzymatic reactions whose end product chorismate is the precursor for the synthesis of the aromatic amino acids Phe, Tyr and Trp. In fungi and plants, chorismate is a precursor for many specialised metabolites (i.e. secondary metabolites) that play an important role in the plant's interaction with its environment. The shikimate pathway and aromatic amino acid biosynthesis have been extensively studied in a variety of microorganisms, fungi and plants. Furthermore, the dual involvement of the shikimate and aromatic amino acid biosynthesis pathways in central and specialised metabolism still raises major questions regarding the genes and enzymes involved, and their control, their evolutionary origins and coordinated regulation with genes of associated pathways in response to altered environmental conditions and diverse developmental programs.

Key Concepts:

  • The shikimate pathway is the only known pathway for biosynthesis of chorismate and the aromatic amino acids Phe, Tyr and Trp.

  • The shikimate pathway is a bridge between central metabolism and specialised metabolism.

  • The shikimate pathway occurs in various groups of microorganisms, plants and parasites, whereas it does not occur in animals.

  • The pathway enzymes are being targeted for antimicrobial drug and herbicide design.

  • Shikimic acid is an essential metabolite that may balance the metabolic status of the pathway.

  • Chorismate is a branch point metabolite for aromatic amino acids and phenolic compounds.

  • This is an ancient eukaryotic pathway which has been subject to diverse evolutionary processes.

  • Several enzymes from these pathways are allosterically regulated by their end products: Phe, Tyr or Trp.

  • The shikimate pathway and aromatic amino acids, and the specialised metabolites derived from them, simultaneously respond to rhythmic changes.

Keywords: shikimate; chorismate; phenylalanine; tyrosine; tryptophan; central metabolism; specialised metabolites; secondary metabolites

Figure 1.

The shikimate pathway. Numbers indicate individual enzymes. Their names, substrates and products are given in Table .

Figure 2.

The aromatic amino acid biosynthesis. Numbers indicate individual enzymes. Their names, substrates and products are given in Table .

Figure 3.

Major classes of specialised metabolites derived from shikimate, chorismate, Phe, Tyr and Tryptophan.



Arcuri HA, Zafalon GF, Marucci EA et al. (2010) SKPDB: A structural database of shikimate pathway enzymes. BMC Bioinformatics 11: 12.

Bekal S, Niblack T and Lambert K (2003) A chorismate mutase from the soybean cyst nematode Heterodera glycines shows polymorphisms that correlate with virulence. Molecular Plant‐Microbe Interactions 16: 439–446.

Borevitz JO, Xia Y, Blount J, Dixon RA and Lamb C (2000) Activation tagging identifies a conserved MYB regulator of phenylpropanoid biosynthesis. Plant Cell 12(12): 2383–2394.

Buehring NW, Massey JH and Reynolds DB (2007) Shikimic acid accumulation in field‐grown corn (Zea mays) following simulated glyphosate drift. Journal of Agricultural and Food Chemistry 55(3): 819–824.

Chen Y, Zhang X, Wu W et al. (2006) Overexpression of the wounding‐responsive gene AtMYB15 activates the shikimate pathway in Arabidopsis. Journal of Integrative Plant Biology 48(9): 1084–1095.

Cho M, Corea O, Yang H et al. (2007) Phenylalanine biosynthesis in Arabidopsis thaliana identification and characterization of arogenate dehydratases. Journal of Biological Chemistry 282(42): 30827–30835.

Connelly JA and Conn EE (1986) Tyrosine biosynthesis in Sorghum bicolor: isolation and regulatory properties of arogenate dehydrogenase. Zeitschrift für Naturforschung C 41(1‐2): 69–78.

Dal Cin V, Tieman DM, Tohge T et al. (2011) Identification of genes in the phenylalanine metabolic pathway by ectopic expression of a MYB transcription factor in tomato fruit. Plant Cell 23(7): 2738–2753.

Davis EL, Hussey RS, Mitchum MG and Baum TJ (2008) Parasitism proteins in nematode‐plant interactions. Current Opinion in Plant Biology 11(4): 360–366.

Ding L, Hofius D, Hajirezaei MR et al. (2007) Functional analysis of the essential bifunctional tobacco enzyme 3‐dehydroquinate dehydratase/shikimate dehydrogenase in transgenic tobacco plants. Journal of Experimental Botany 58(8): 2053–2067.

Doyle EA and Lambert KN (2003) Meloidogyne javanica chorismate mutase 1 alters plant cell development. Molecular Plant‐Microbe Interactions 16(2): 123–131.

Duke SO and Powles SB (2008) Glyphosate: a once‐in‐a‐century herbicide. Pest Management Science 64(4): 319–325.

Gientka I and Duszkiewicz‐Reinhard W (2009) Shikimate pathway in yeast cells: enzymes, functioning, regulation – a review. Polish Journal of Food and Nutrition Sciences 59(2): 113–118.

Gilchrist D and Kosuge T (1980) Aromatic amino acid biosynthesis and its regulation. In: Miflin BN (ed.) The Biochemistry of Plants, vol 5, pp. 507–531. New York: Academic Press.

Graindorge M, Giustini C, Jacomin AC et al. (2010) Identification of a plant gene encoding glutamate/aspartate‐prephenate aminotransferase: the last homeless enzyme of aromatic amino acids biosynthesis. FEBS Letters 584(20): 4357–4360.

Graziana A and Boudet A (1980) 3‐deoxy‐D‐arabino‐heptulosonate 7‐phosphate synthase from Zea mays: general properties and regulation by tryptophan. Plant and Cell Physiology 21: 793–802.

Haslam E (1993) Shikimic Acid Metabolism and Metabolites, pp 157–168. New York: John Wiley and Sons.

Herrmann KM (1995) The shikimate pathway: early steps in the biosynthesis of aromatic compounds. Plant Cell 7(7): 907–919.

Herrmann KM and Weaver LM (1999) The shikimate pathway. Annual Review of Plant Physiology and Plant Molecular Biology 50: 473–503.

Hoffmann L, Besseau S, Geoffroy P et al. (2004) Silencing of hydroxycinnamoy‐coenzyme A shikimate/quinate hydroxycinnamoyltransferase affects phenylpropanoid biosynthesis. Plant Cell 16(6): 1446–1465.

Hu C, Jiang P, Xu J, Wu Y and Huang W (2003) Mutation analysis of the feedback inhibition site of phenylalanine‐sensitive 3‐deoxy‐D‐arabino‐heptulosonate 7‐phosphate synthase of Escherichia coli. Journal of Basic Microbiology 43(5): 399–406.

Hughes EH, Hong SB, Gibson SI, Shanks JV and San KY (2004) Metabolic engineering of the indole pathway in Catharanthus roseus hairy roots and increased accumulation of tryptamine and serpentine. Metabolic Engineering 6(4): 268–276.

Ikeda M (2006) Towards bacterial strains overproducing L‐tryptophan and other aromatics by metabolic engineering. Applied Microbiology and Biotechnology 69(6): 615–626.

Ishihara A, Asada Y, Takahashi Y et al. (2006) Metabolic changes in Arabidopsis thaliana expressing the feedback‐resistant anthranilate synthase alpha subunit gene OASA1D. Phytochemistry 67(21): 2349–2362.

Kaminaga Y, Schnepp J, Peel G et al. (2006) Plant phenylacetaldehyde synthase is a bifunctional homotetrameric enzyme that catalyzes phenylalanine decarboxylation and oxidation. Journal of Biological Chemistry 281(33): 23357–23366.

Less H and Galili G (2008) Principal transcriptional programs regulating plant amino acid metabolism in response to abiotic stresses. Plant Physiology 147(1): 316–330.

Luttik MA, Vuralhan Z, Suir E et al. (2008) Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis: quantification of metabolic impact. Metabolic Engineering 10(3‐4): 141–153.

Maeda H, Shasany AK, Schnepp J et al. (2010) RNAi suppression of arogenate dehydratase1 reveals that phenylalanine is synthesized predominantly via the arogenate pathway in Petunia petals. Plant Cell 22: 832–849.

Maeda H, Yoo H and Dudareva N (2011) Prephenate aminotransferase directs plant phenylalanine biosynthesis via arogenate. Nature Chemical Biology 7(1): 19–21.

Merino E, Jensen RA and Yanofsky C (2008) Evolution of bacterial trp operons and their regulation. Current Opinion in Microbiology 11(2): 78–86.

Mobley E, Kunkel B and Keith B (1999) Identification, characterization and comparative analysis of a novel chorismate mutase gene in Arabidopsis thaliana. Gene 240: 115–123.

Mueller TC, Massey JH, Hayes RM, Main CL and Stewart CN Jr (2003) Shikimate accumulates in both glyphosate‐sensitive and glyphosate‐resistant horseweed (Conyza canadensis L Cronq.). Journal of Agricultural and Food Chemistry 51(3): 680–684.

Mustafa NR and Verpoorte R (2005) Chorismate derived C6C1 compounds in plants. Planta 222(1): 1–5.

Niyogi KK, Last RL, Fink GR and Keith B (1993) Suppressors of trp1 fluorescence identify a new Arabidopsis gene, TRP4, encoding the anthranilate synthase beta subunit. Plant Cell 5(9): 1011–1027.

Pinto JE, Suzich JA and Herrmann KM (1986) 3‐deoxy‐d‐arabino‐heptulosonate 7‐phosphate synthase from potato tuber (Solanum tuberosum L.). Plant Physiology 82(4): 1040–1044.

Pline WA, Wilcut JW, Duke SO, Edmisten KL and Wells R (2002) Tolerance and accumulation of shikimic acid in response to glyphosate applications in glyphosate‐resistant and nonglyphosate‐resistant cotton (Gossypium hirsutum L.). Journal of Agricultural and Food Chemistry 50(3): 506–512.

Pollegioni L, Schonbrunn E and Siehl D (2011) Molecular basis of glyphosate resistance‐different approaches through protein engineering. FEBS Journal 278(16): 2753–2766.

Popeijus H, Blok V, Cardle L et al. (2000) Analysis of genes expressed in second stage juveniles of the potato cyst nematodes Globodera rostochiensis and Globodera pallida using the expressed sequence tag approach. Nematology 2: 567–574.

Pribat A, Noiriel A, Morse AM et al. (2010) Nonflowering plants possess a unique folate‐dependent phenylalanine hydroxylase that is localized in chloroplasts. Plant Cell 22(10): 3410–3422.

Reinink M and Borstap A (1982) 3‐deoxy‐d‐arabino‐heptulosonate 7‐phosphate synthase from pea leaves: inhibition by L‐tyrosine. Plant Science Letters 26: 167–171.

Richards TA, Dacks JB, Campbell SA et al. (2006) Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements. Eukaryotic Cell 5(9): 1517–1531.

Rippert P and Matringe M (2002) Purification and kinetic analysis of the two recombinant arogenate dehydrogenase isoforms of Arabidopsis thaliana. European Journal of Biochemistry 269(19): 4753–4761.

Rippert P, Puyaubert J, Grisollet D, Derrier L and Matringe M (2009) Tyrosine and phenylalanine are synthesized within the plastids in Arabidopsis. Plant Physiology 149: 1251–1260.

Rubin JL and Jensen RA (1985) Differentially regulated isozymes of 3‐deoxy‐d‐arabino‐heptulosonate‐7‐phosphate synthase from seedlings of Vigna radiata [L] Wilczek. Plant Physiology 7(3): 711–718.

Schuurink RC, Haring MA and Clark DG (2006) Regulation of volatile benzenoid biosynthesis in Petunia flowers. Trends in Plant Science 11(1): 20–25.

Spitzer‐Rimon B, Marhevka E, Barkai O et al. (2010) EOBII, a gene encoding a flower‐specific regulator of phenylpropanoid volatiles’ biosynthesis in Petunia. Plant Cell 22: 1961–1976.

Sprenger G (2006) Aromatic Amino Acids. Berlin, Germany: Springer‐Verlag.

Suzich J, Ranjeva R, Hasegawa P and Herrmann K (1984) Regulation of the shikimate pathway of carrot cells in suspension culture. Plant Physiology 75: 369–371.

Tozawa Y, Hasegawa H, Terakawa T and Wakasa K (2001) Characterization of rice anthranilate synthase alpha‐subunit genes OASA1 and OASA2. Tryptophan accumulation in transgenic rice expressing a feedback‐insensitive mutant of OASA1. Plant Physiology 126(4): 1493–1506.

Tzin V and Galili G (2010) New Insights into the shikimate and aromatic amino acids biosynthesis pathways in plants. Molecular Plant 3(6): 956–972.

Tzin V, Malitsky S, Aharoni A and Galili G (2009) Expression of a bacterial bi‐functional chorismate mutase/prephenate dehydratase modulates primary and secondary metabolism associated with aromatic amino acids in Arabidopsis. Plant Journal 60(1): 156–167.

Tzin V, Malitsky S, Moyal Ben Zvi M et al. (2012) Expression of a bacterial feedback‐insensitive DAHP synthase of the shikimate pathway in Arabiodlopsis elucidated potential metabolic bottlenecks between primary and Secondary metabolism. New Phytologist 194(2): 430–439.

Vivancos PD, Driscoll SP, Bulman CA et al. (2011) 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 Physiology 157(1): 256–268.

Watanabe S, Hayashi K, Yagi K et al. (2002) Biogenesis of 2‐phenylethanol in rose flowers: incorporation of [2H8]L‐phenylalanine into 2‐phenylethanol and its beta‐D‐glucopyranoside during the flower opening of Rosa ‘Hoh‐Jun’ and Rosa damascena Mill. Bioscience, Biotechnology, and Biochemistry 66(5): 943–947.

Weber A, Schwacke R and Flügge U (2005) Solute transporters of the plastid envelope membrane. Annual Review of Plant Biology 56: 133–164.

Yamada T, Matsuda F, Kasai K et al. (2008) Mutation of a rice gene encoding a phenylalanine biosynthetic enzyme results in accumulation of phenylalanine and tryptophan. Plant Cell 20(5): 1316–1329.

Zybailov B, Rutschow H, Friso G et al. (2008) Sorting signals, N‐terminal modifications and abundance of the chloroplast proteome. PLoS One 3(4): e1994.

Further Reading

Gosset G (2009) Production of aromatic compounds in bacteria. Current Opinion in Biotechnology 20(6): 651–658.

Kramer M, Bongaerts J, Bovenberg R et al. (2003) Metabolic engineering for microbial production of shikimic acid. Metabolic Engineering 5(4): 277–283.

Rippert P, Scimemi C, Dubald M and Matringe M (2004) Engineering plant shikimate pathway for production of tocotrienol and improving herbicide resistance. Plant Physiology 134(1): 92–100.

Starcevic A, Akthar S, Dunlap WC et al. (2008) Enzymes of the shikimic acid pathway encoded in the genome of a basal metazoan, Nematostella vectensis, have microbial origins. Proceedings of the National Academy of Sciences of the USA 105(7): 2533–2537.

Vanholme B, Kast P, Haegeman A et al. (2009) Structural and functional investigation of a secreted chorismate mutase from the plant‐parasitic nematode Heterodera schachtii in the context of related enzymes from diverse origins. Molecular Plant Pathology 10(2): 189–200.

Velini ED, Alves E, Godoy MC et al. (2008) Glyphosate applied at low doses can stimulate plant growth. Pest Management Science 64(4): 489–496.

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Tzin, Vered, Galili, Gad, and Aharoni, Asaph(Aug 2012) Shikimate Pathway and Aromatic Amino Acid Biosynthesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001315.pub2]