Monooxygenations

Xenobiotics metabolism, 1, 223-225 monooxygenation cytochrome P450 in, 1, 259-260 Xenon... 

Figure 5.49 (a) Total-ion-current trace, and (b) the reconstructed ion chromatogram of mjz 510.2 0.5 (monooxygenated metabolites) from LC-MS analysis of human microsomal incubation of Glyburide. Reprinted with permission from Zhang, H., Henion, J., Yang, Y. and Spooner, N., Anal. Chem., 72, 3342-3348 (2000). Copyright (2000) American Chemical Society. 

FIGURE 2.4 Proposed mechanism for monooxygenation by cytochrome P450. 

Toluene/o-xylene monooxygenase in P. stutzeri strain 0X1 carried ont snccessive monooxygenation of o-xylene (Bertoni et al. 1998), and the tolnene-4-monooxygenase of Pseudomonas mendocina KRl and tolnene-3-monooxygenase of Ralstonia pickettii PKOl can hydroxylate benzene, tolnene, and o-xylene (Tao et al. 2004 Vardar and Wood 2004). 

When 1,4-dihydroxy compounds are produced by monooxygenation, these are degraded by the gentisate pathway (Figure 3.13) mediated by gentisate dioxygenase (Wergath et al. 1998). 

The transformations of a- and p-endosulfan with the elimination of sulfite are carried out by flavin-dependent monooxygenation in Mycobacterium sp. (Sntherland et al. 2002) and Arthrobacter sp. (Weir et al. 2006). 

FIGURE 3.19 Cytochrome P450 monooxygenation of (a) lanosterol, (b) aromatization of A -3-ketosterols, and (c) pregnenolone. 

Arene hydrocarbon dioxygenases are capable of carrying out a number of reactions other than the introduction of both atoms of oxygen into the substrate. Illustrative examples of monooxygenation carried out by dioxygenases include the following ... 

Gibson DT, Resnick SM, Lee K, Brand JM, Torok DS, Wackett LP, Schocken MJ, Haigler BE (1995) Desaturation, dioxygenation, and monooxygenation reactions catalysed by naphthalene dioxygenase from Pseudomonas sp. strain 9S16-4. J Bacteriol 111 2615-2621. 

Lehning A, U Fgock, R-M Wittich, KN Trmmis, DH Pieper (1997) Metabolism of chlorotoluenes by Burk-holderia sp. strain PS12 and toluene dioxygenase of Pseudomonas putida FI evidence for monooxygenation by toluene and chlorobenzene dioxygenases. Appl Environ Microbiol 63 1974-1979. 

Rosche B, B Tshisuaka, B Hauer, F Lingens, S Fetzner (1997) 2-Oxo-l,2-dihydroquinoline 8-monooxygen-ase phylogenetic relationship to other multicomponent nonheme iron oxygenases. J Bacterial 179 3549-3554. 

Suske WA, WJH van Berkel, H-P Kohler (1999) Catalytic mechanism of 2-hydroxybiphenyl 3-monooxygen-ase a flavoprotein from Pseudomonas azelaica HBPl. J Biol Chem 274 33355-33365. 

Wackett LP, LD Kwart and DT Gibson (1988) Benzylic monooxygenation catalyzed by toluene dioxygenase from Pseudomonas putida. Biochemistry 27 1360-1367. 

Zhou N-Y, A Jenkins, CKN Chan, KW Chion, DJ Leak (1999) The alkene monooxygenase from Xanthobacter strain Py2 is closely related to aromatic monooxygenases and catalyzes aromatic monooxygenation of benzene, toluene, and phenol. Appl Environ Microbiol 65 1589-1595. 

During the degradation of 2-chloroacetophenone by a strain of Alcaligenes sp., one atom of 02 was incorporated into 2-chlorophenol formed from the 2-chlorophenyl acetate that was initially formed by Baeyer-Villiger monooxygenation (Higson and Focht 1990). 

The degradation of acenaphthene is initiated by benzylic monooxygenation, and the pathway was determined using [l- C]acenaphthene by the isolation of intermediate metabolites (Selifonov et al. 1998). Importantly, the method proved applicable even when only limited biotransformation of the substrates had taken place by partial oxidation. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Noncyanogenic fungi can degrade cyanide to formamide followed by hydrolysis by a hydratase to formate and ammonia (Dumestre et al. 1997). This pathway is also used by some bacteria (Jandyala et al. 2003). Bacteria also use a number of reactions for the detoxification of cyanide, including monooxygenation to COj and ammonia (Wang et al. 1996). 

Hage JC, S Hartmans (1999) Monooxygenation-mediated 1,2-dichloroethane degradation by Pseudomonas sp. strain DCAl. Appl Environ Microbiol 65 2466-2470. 

---