関: shikimate

WordNet

street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"

PrepTutorEJDIC

酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/07 14:02:31」(JST)

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Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi (シキミ, Illicium anisatum), from which it was first isolated.

Shikimic acid is a precursor for:

the aromatic amino acids phenylalanine and tyrosine
indole, indole derivatives and aromatic amino acid tryptophan
many alkaloids and other aromatic metabolites
phenylpropanoids, flavonoids, tannins, and lignin.

In the pharmaceutical industry, shikimic acid from the Chinese star anise 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 fruit, which is abundant in North America, in yields of around 1.5%. For example, 4 kg 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.^[1]^[2]^[3] A 2010 study released by the University of Maine showed that shikimic acid can also be readily harvested from the needles of several varieties of pine tree.^[4]

Shikimate can be used to synthesise (6S)-6-Fluoroshikimic acid, ^[5] an antibiotic which inhibits the aromatic biosynthetic pathway. ^[6]

Biosynthesis

Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP), in a reaction catalyzed by the enzyme DAHP synthase. DAHP is then transformed to 3-dehydroquinate (DHQ), in a reaction catalyzed by DHQ synthase. Although this reaction requires nicotinamide adenine dinucleotide (NAD) as a cofactor, the enzymic mechanism regenerates it, resulting in the net use of no NAD.

Biosynthesis of 3-dehydroquinate from phosphoenolpyruate and erythrose-4-phosphate

DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme dehydroquinase, which is reduced to shikimic acid by the enzyme shikimate dehydrogenase, which uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor.

Biosynthesis of shikimic acid from 3-dehydroquinate

Shikimate pathway

The shikimate pathway is a seven step metabolic route used by bacteria, fungi, algae, parasites and plants for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan). This pathway is not found in animals and in humans, hence the products of this pathway represent essential amino acids that must be obtained from the animal's diet.

The first enzyme involved is the shikimate kinase, an enzyme that catalyzes the ATP-dependent phosphorylation of shikimate to form shikimate 3-phosphate.^[7] Shikimate 3-phosphate is then coupled with phosphoenol pyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase.

Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a chorismate synthase.

Prephenic acid is then synthesized by a rearrangement of chorismate.^[8]^[9]

Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.

Books

The shikimate pathway, E. Haslam, 2 editions - first published in 1974
Shikimic acid, E. Haslam, 1 edition - first published in 1993

References

^ Bradley, David (December 2005). "Star role for bacteria in controlling flu pandemic?" (html). Nature Reviews Drug Discovery 4 (12): 945–946. doi:10.1038/nrd1917. PMID 16370070. http://www.nature.com/nrd/journal/v4/n12/full/nrd1917.html. Retrieved 2007-03-07.
^ Marco Krämer, Johannes Bongaertsa, Roel Bovenberga, Susanne Kremera, Ulrike Müllera, Sonja Orfa, Marcel Wubboltsa, Leon Raevena. (2003). "Metabolic engineering for microbial production of shikimic acid". Metabolic Engineering 5 (4): 277–283. doi:10.1016/j.ymben.2003.09.001. PMID 14642355. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WN3-49WPJRH-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b969b390767333c6e332d2ec9067cc4e.
^ Johansson Louise, Lindskog Anna, Silfversparre Gustav, Cimander Christian, Nielsen Kristian Fog, Liden Gunnar (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. PMID 16240440.
^ Maine pine needles yield valuable Tamiflu material, Boston.com, November 7, 2010
^ http://jiang.tju.edu.cn/pdfs/6flufull.pdf
^ http://aac.asm.org/content/38/2/403.full.pdf
^ 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. PMID 15012217. edit
^ Helmut Goerisch (1978). "On the mechanism of the chorismate mutase reaction". Biochemistry 17 (18): 3700. doi:10.1021/bi00611a004.
^ Peter Kast, Yadu B. Tewari, Olaf Wiest, Donald Hilvert, Kendall N. Houk, and Robert N. Goldberg (1997). "Thermodynamics of the Conversion of Chorismate to Prephenate: Experimental Results and Theoretical Predictions". J. Phys. Chem. B 101 (50): 10976–10982. doi:10.1021/jp972501l.

External links

Shikimate and chorismate biosynthesis

UpToDate Contents

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English Journal

Shikimic acid, a base compound for the formulation of swine/avian flu drug: statistical optimization, fed-batch and scale up studies along with its application as an antibacterial agent.

Tripathi P1, Rawat G, Yadav S, Saxena RK.
Antonie van Leeuwenhoek.Antonie Van Leeuwenhoek.2015 Feb;107(2):419-31. doi: 10.1007/s10482-014-0340-z. Epub 2014 Nov 25.
The sudden outbreak of swine flu has increased the global demand of shikimic acid which is an industrially interesting compound, as it is used as a key starting material for the synthesis of a neuraminidase inhibitor Tamiflu(®), for the treatment of antiviral infections such as swine flu. Statistic
PMID 25563634

Protein kinase GCN2 mediates responses to glyphosate in Arabidopsis.

Faus I, Zabalza A, Santiago J, Nebauer SG, Royuela M, Serrano R, Gadea J.
BMC plant biology.BMC Plant Biol.2015 Jan 21;15(1):14. [Epub ahead of print]
BackgroundThe increased selection pressure of the herbicide glyphosate has played a role in the evolution of glyphosate-resistance in weedy species, an issue that is becoming a threat to global agriculture. The molecular components involved in the cellular toxicity response to this herbicide at the
PMID 25603772

Irreversible covalent modification of type I dehydroquinase with a stable Schiff base.

Tizón L1, Maneiro M, Peón A, Otero JM, Lence E, Poza S, van Raaij MJ, Thompson P, Hawkins AR, González-Bello C.
Organic & biomolecular chemistry.Org Biomol Chem.2015 Jan 21;13(3):706-16. doi: 10.1039/c4ob01782j.
The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of the shikimic acid pathway, is investigated by structural, biochemical and computational studies. Two epoxides, which are mimetics of the natural substrate, were designed as irreversible inhibitors of the DHQ1 enzyme and
PMID 25370445

Japanese Journal

フラボノイドの代謝マップ

西條了康
茶業研究報告 (114), 79-88, 2012-12
NAID 40019577485

New phenolic compounds from Meehania urticifolia

Murata Toshihiro,Miyase Toshio,Yoshizaki Fumihiko
Journal of natural medicines 65(2), 385-390, 2011-04-20
NAID 10029461584

Metabolite profiling of Raphanus sativus L. to evaluate the effects of manure amendment(Plant Nutrition)

Okazaki Keiki,Shinano Takuro,Oka Norikuni [他],TAKEBE Masako
Soil science and plant nutrition 56(4), 591-600, 2010-08
… With increased amounts of applied manure, the concentrations of malic acid, myo-inositol-phosphate and sucrose decreased, whereas the concentrations of shikimic acid, arabinose and L-methionine increased. …
NAID 110008144357

Related Pictures

★リンクテーブル★

リンク元	「シキミ酸」「shikimate」

「シキミ酸」

Shikimic acid
	IUPAC name (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid
Identifiers
CAS number	138-59-0
PubChem	8742
ChemSpider	8412
EC number	205-334-2
KEGG	C00493
ChEBI	CHEBI:16119
ChEMBL	CHEMBL290345
Jmol-3D images	Image 1
	SMILES C1[C@H]([C@@H]([C@@H](C=C1C(=O)O)O)O)O ;
	InChI InChI=1S/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1 ; Key: JXOHGGNKMLTUBP-HSUXUTPPSA-N InChI=1/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1/f/h11H InChI=1/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1; Key: JXOHGGNKMLTUBP-HSUXUTPPBZ ;
Properties
Molecular formula	C7H10O5
Molar mass	174.15 g mol−1
Melting point	185–187 °C
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references