Dehydroquinate dehydratase

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [111.1, Scheme 3.111] as the butane-2,3-diace-tal 111.2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase. Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111.1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase and influenza neuraminadase - as well as shikimic acid derivatives. ... 

The reversible conversion of dehydroquinate to dehydroshikimate is catalyzed by 3-dehydroquinate dehydratase [Fig. 2 (3)]. The occurrence of this enzyme in plants was inferred by the work of Nandy and Ganguli (I%1) who reported that dehydroshikimate was a product in the incubation of erythrose-4-P and phosphoenolpyruvate with Phaseolus aureus extracts. Later the activity of the enzyme was found in several plant cell cultures and several plant sources (Minamikawaal., 1968 Balinsky and Davies, 1962). Balinsky and Davies (l%lc) partially purified the enzyme and studied its properties. There are reports that the enzyme occurs aggregated with shiki-mate dehydrogenase in a variety of plants including both monocots and dicots (Koshiba, 1978 Koshiba and Yoshida, 1976 Boudet and Lecussan, 1974 Boudet, et al., 1975). Monocots also contain a second unaggregated... 

In the next step of the sequence, 3-dehydroquinate (4) is dehydrated via a Z-elimination to produce 3-dehydroshiki-mate (5). This reaction is catalyzed by 3-dehydroquinate dehydratase. 3-Dehydroshikimate (5) is, in turn, reduced to shikimate (6) by 3-dehydroshikimate reductase, an enzyme that requires NADPH as a cofactor. Shikimate (6) is then converted to the 3-phosphate (7) by the action of shikimate kinase and ATP. 

Scheme 11.81. A proposed pathway from 3-dehydroquinate to 3-dehydroshikimate with 3-dehydroquinate dehydratase (EC 4.2.1.10) serving as the catalyzing enzyme.The suggestion of the mechanism follows Gourley, D. G. Shrive, A. K. Pohkarpov, I. Krell.T Coggins, J. R. Hawkins, A. R. Isaccs,N. W. Sawyer, L. Nat. Struct. Biol, 1999,6,521. ENZ = 3-dehydroquinate dehydratase (EC 4.2.1.10).

Enzymes involved as catalysts in each of the steps from 3-dehydro-quinate (10) to chorismate (14) in the conunon pathway have all been subsequently isolated and characterised from bacterial mutants. Methods of assay for each form of activity have been described . Mitsuhashi and Davis first isolated 3-dehydroquinate dehydratase (E.C. 4.1.2.10) the enzyme which is responsible for the dehydration step (10 11). With a partially purified extract they showed that the... 

The reactions of the shikimate pathway pose a number of interesting questions of both a mechanistic and stereochemical nature. Detailed studies have been made of the DAHP synthetase, 3-dehydroquinate dehydratase, 5-enolpyruvylshikimate-3-phosphate synthetase and chorismate synthetase reactions which have added further important knowledge to this area of molecular biology. Whilst these investigations have done nothing to detract from the important dictum that cells obey the laws of chemistry , they have nevertheless revealed some of the distinctive facets of enzyme chemistry and have highlighted some of the important differences between enzyme and relat chemically catalysed reactions. 

Figure 1.8. Determination of the stereochemical features of the 3-dehydroquinate dehydratase reaction ...

The cis elimination and addition of water observed in the reversible 3-dehydroquinate dehydratase reaction represents the first example of this type recorded in enzyme chemistry. It contrasts with the known tram addition of water to other similar afi unsaturated compounds such as m-aconitate and fumarate Hanson and Rose formulated the addition as taking place in two distinct steps. First addition of water (or hydroxide anion) to give the enol or enolate anion (28) followed by protonation of the enol at the a... 

Mogi T, Ano Y, Nakatsuka T, Toyama H, Muroi A, Miyoshi H, Migita CT, Ui H, Shiomi K, Omura S, Kita K, Matsushita K (2009) Biochemical and spectroscopic properties of cyanide-insensitive quinol oxidase from Gluconobacter oxydans. J Biochem (Tokyo) 146 263-271 Nishikura-Imamura S, Matsutani M, Insomphun C, Vangnai AS, Toyama H, Yakushi T, Abe T, Adachi O, Matsushita K (2014) Overexpression of a type II 3-dehydroquinate dehydratase enhances the biotransformation of quinate to 3-dehydroshildmate in Gluconobacter oxydans. Appl Microbiol Biotechnol 98 2955-2963... 

Adachi O, Ano Y, Toyama H, Matsushita K (2008b) A novel 3-dehydroquinate dehydratase catalyzing extracellular formation of 3-dehydroshikimate by oxidative fermentation of Gluconobacter oxydans IFO 3244. Biosci Biotechnol Biochem 72(6) 1475-1482. Epub 2008 Jun 7... 

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