Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi (シキミ, the Japanese star anise, Illicium anisatum), from which it was first isolated in 1885 by Johan Fredrik Eykman.[1] The elucidation of its structure was made nearly 50 years later.[2]
Mycosporine-like amino acids are small secondary metabolites produced by organisms that live in environments with high volumes of sunlight, usually marine environments.
In the pharmaceutical industry, shikimic acid from the Chinese star anise (Illicium verum) is used as a base material for production of oseltamivir (Tamiflu). Although shikimic acid is present in most autotrophic organisms, it is a biosynthetic intermediate and in general found in very low concentrations. The low isolation yield of shikimic acid from the Chinese star anise is blamed for the 2005 shortage of oseltamivir. Shikimic acid can also be extracted from the seeds of the sweetgum (Liquidambar styraciflua) fruit,[2] which is abundant in North America, in yields of around 1.5%. For example, 4 kg (8.8 lb) of sweetgum seeds is needed for fourteen packages of Tamiflu. By comparison, star anise has been reported to yield 3% to 7% shikimic acid. Biosynthetic pathways in E. coli have recently been enhanced to allow the organism to accumulate enough material to be used commercially.[7][8][9] A 2010 study released by the University of Maine showed that shikimic acid can also be readily harvested from the needles of several species of pine tree.[10]
Protecting groups are more commonly used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to the process. However, the availability of a cheap chiral building block can overcome these additional costs, for example, shikimic acid for oseltamivir.
Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of oseltamivir.
It occurs in tree fern fronds, a specialty called fiddlehead (furled fronds of a young tree fern in the order Cyatheales, harvested for use as a vegetable). These fronds are edible, but can be roasted to remove shikimic acid.[14]
^ abEnrich, Liza B.; Scheuermann, Margaret L.; Mohadjer, Ashley; Matthias, Kathryn R.; Eller, Chrystal F.; Newman, M. Scott; Fujinaka, Michael; Poon, Thomas (April 2008). "Liquidambar styraciflua: a renewable source of shikimic acid". Tetrahedron Letters. 49 (16): 2503–2505. doi:10.1016/j.tetlet.2008.02.140.
^Herrmann, K. M.; Weaver, L. M. (1999). "The Shikimate Pathway". Annual Review of Plant Physiology and Plant Molecular Biology. 50: 473–503. doi:10.1146/annurev.arplant.50.1.473. PMID15012217.
^Kast, P.; Tewari, Y. B.; Wiest, O.; Hilvert, D.; Houk, K. N.; Goldberg, Robert N. (1997). "Thermodynamics of the Conversion of Chorismate to Prephenate: Experimental Results and Theoretical Predictions". Journal of Physical Chemistry B. 101 (50): 10976–10982. doi:10.1021/jp972501l.
^Bradley, D. (December 2005). "Star role for bacteria in controlling flu pandemic?". Nature Reviews Drug Discovery. 4 (12): 945–946. doi:10.1038/nrd1917. PMID16370070. S2CID30035056.
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Krämer, M.; Bongaerts, J.; Bovenberg, R.; Kremer, S.; Müller, U.; Orf, S.; Wubbolts, M.; Raeven, L. (2003). "Metabolic engineering for microbial production of shikimic acid". Metabolic Engineering. 5 (4): 277–283. doi:10.1016/j.ymben.2003.09.001. PMID14642355.
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Johansson, L.; Lindskog, A.; Silfversparre, G.; Cimander, C.; Nielsen, K. F.; Liden, G. (2005). "Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate-limited and carbon-limited conditions". Biotechnology and Bioengineering. 92 (5): 541–552. doi:10.1002/bit.20546. PMID16240440. S2CID19659961.
^Chung, Hai-Jung (30 September 2009). "Evaluation of the Biological Activity of Extracts from Star-Anise (Illicium verum)". Preventive Nutrition and Food Science. 14 (3): 195–200. doi:10.3746/jfn.2009.14.3.195.
