Dihydrodiol dehydrogenase

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

Rogers JE, DT Gibson (1977) Purification and properties of cw-toluene dihydrodiol dehydrogenase from Pseudomonas putida. J Bacterial 130 1117-1124. 

Patel TR, DT Gibson (1974) Purification and properties of (+)-cZ5-naphthalene dihydrodiol dehydrogenase of Pseudomonas putida. Bacteriol 119 879-888. 

Degradation of PCBs is carried out by a suite of enzymes comprising biphenyl-2,3-dioxygenase, biphenyl-2,3-dihydrodiol dehydrogenase, 2,3-dihydroxybiphenyl dioxygenase, and the hydrolytic enzymes that produce benzoate encoded by the genes bphA, bphB, bphC, and bphD (Furukawa and Miyazaki 1986 Ahmad et al. 1991 Taira et al. 1992). 

Pollmann K, S Beil, DH Pieper (2001) Transformation of chlorinated benzenes and toluenes by Ralstonia sp. strain PS 12 tecA (tetrachlorobenzene dioxygenase) and tecB (chlorobenzene dihydrodiol dehydrogenase) gene products. Appl Environ Microbiol 67 4057 063. 

Ohara H, Miyabe Y, DeyashiM Y, et al. Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver. Biochem Pharmacol 1995 50(2) 221-227. 

Dihydro-1,2-dihydroxybenzene (10.13) is oxidized by dihydrodiol dehydrogenase (EC 1.3.1.20) to catechol (10.15) (Chapt. 4 in [la]) [76], In a typical experiment in which 10.13 is incubated with phenobarbital-induced rabbit liver microsomes, phenol (10.14), catechol (10.15), and hydroquinone (10.16) represent 54, 39, and 1%, respectively, of the total metabolites detected [75]. In other words, neither benzene oxide (10.1) nor its hydration product l,2-dihydro-l,2-dihydroxybenzene (10.13) was detected. 

K. Vogel, K. L. Platt, P. Petrovic, A. Seidel, F. Oesch, Dihydrodiol Dehydrogenase Substrate Specificity, Inducibility and Tissue Distribution , Arch. Toxicol. 1982, Suppl. 5, 360 - 364. 

DEWAR STRUCTURES KEKULE STRUCTURES c/s-Benzene dihydrodiol dehydrogenase,... 

Hoog SS, Pawlowski JE, Alzari PM, Penning TM, Lewis M. Three-dimensional structure of rat liver -hydroxysteroid/dihydrodiol dehydrogenase a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci USA 1994 91 2517-2521. 

The mandelate and jS-ketoadipate pathways are a good example of gene duplication, with strong evidence of the former evolving from the latter the congruence of MR and MLE, (S)-ManDH and benzoate dihydrodiol dehydrogenase, and possibly benzoyl formate decarboxylase and protocatechuate decarboxylase. 

Evolution of MR from MLE and possibly (S)-ManDH from benzoate dihydrodiol dehydrogenase points to the relevance of the enzyme mechanism for catalytic reactivity. If the chemistry is right, the remaining necessary enhancement of specificity, i.e., the enhancement of binding of substrate, is the simpler task, in contrast to the procedure for design of catalytic antibodies. 

Penning, T. M., Burczynski, M. E., Hung, C.-F. et at. (1999). Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation generation of reactive and redox active o-qurnones. Chemical Research in Toxicology, 12, 1—18. 

Abbreviations CYP, cytochrome P450 FMO, flavin monooxygenase GT, glucuronyl transferase EH, epoxide hydrolase AD, alcohol/aldehyde dehydrogenase ES/AM, esterase/amidase MT, methyl transferase ST, sulfotransferase GST, glutathione S-transferase DHD, dihydrodiol dehydrogenase COMT, catechol O-methyltransferase NA, N-actetyl transferase AA, amino acid acyltransferase P-O.P -oxidation. 

Another important group of hydrolytic enzymes are the epoxide hydrolases, also known as epoxide hydrase or epoxide hydratase, most commonly found in liver tissue. Epoxide hydrolases catalyze the hydration of arene oxides and aliphatic epoxides to their corresponding /raKt-dihydrodiols or diols, respectively, by activating a water molecule to attack one of the carbons of the arene oxide or epoxide [41]. Although one of the major metabolites of carbamazepine is the stable epoxide, this metabolite also undergoes hydrolysis to form the trans-dial metabolite (Fig. 3). Likewise, the anticonvulsants phenytoin and mephenytoin form arene oxides, which then form trans-dihy-drodiol that undergo further oxidation to form the catechols by the enzyme dihydrodiol dehydrogenase (Fig. 11) [42,43]. 

The aldo-keto reductases (AKR), a complex superfamily of enzymes, which includes aldehyde reductases (ALR) and dihydrodiol dehydrogenase (DD). 

Dihydrodiols are seldom observed, as are catechol metabolites produced by their dehydrogenation, catalyzed by dihydrodiol dehydrogenase. The further oxidation of phenols and phenolic metabolites to a catechol or hydro-quinone is also possible, the rate of reaction and the nature of products depending on the ring and on the nature and position of its substituents. In a few cases, catechols and hydroquinones have been found to undergo further oxidation to quinones by two single-electron steps. The intermediate in this reaction is a semiquinone. Both quinones and semiquinones are reactive, in particular toward biomolecules, and have been implicated in many toxitication reactions. For example, the high toxicity of benzene in bone marrow is believed to be due to the oxidation of catechol and hydroquinone catalyzed by myeloperoxidase. 

Flowers-Geary, L., Bleczinki, W., Harvey, R. G., and Penning, T. M. (1996). Cytotoxicity and mutagenicity of polycyclic aromatic hydrocarbon ortho-quinones produced by dihydrodiol dehydrogenase. Chem Biol Interact 99, 55-72. 

The naphthalene dihydrodiol dehydrogenase NahB from P. putida strain G7 has been purified as the his-tagged enzyme, and shown to catalyze also the dehydrogenation of biphenyl-2,3-dihydrodiol. biphenyl-3,4-dihydrodiol, and 2,2, 5,5 -tetrachlorobiphenyl-3,4-dihydrodiol (Barriault et al. 1998). In addition, 1,2-dihydroxynaph-thalene dioxygenase carried out extradiol fission of 3,4-dihydrox-ybiphenyl at both the 2,3- and 4,5-positions. 

Dihydrodiol dehydrogenases ( rfms-1,2-dihydrobenzene-1,2-diol NADP oxidoreduc-tase EC 1.3.1.20) are cytosolic enzymes several of which have been characterized. Al-... 

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