Oxygenases flavin-dependent

Anhydrotetracycline oxygenase from Streptomjces aureofaciens which cataly2es the conversion of anhydrotetracycline to dehydrotetracycline, has been isolated and characterized as a flavin-dependent oxygenase (83). It consists of two subunits of mol wt = 57, 500 based on SDS/polyacrylamide—gel electrophoresis. The cosynthetic factor 1 of Streptomjces aureofaciens involved in the reduction of 5a,lla-dehydrochlortetracycline to chlortetracycline, has been identified as 7,8-didemethyl-8-hydroxy-5-deazariboflavin. This work was aided by comparison of spectral data with that of an authentic sample obtained from the hydrolysis of coenzyme F-420 (84). 

Hormann K, JR Andreesen (1991) A flavin-dependent oxygenase reaction initiates the degradation of pyrrole-2-carboxylate in Arthrobacter strain Pyl (DSM 6386). Arch Microbiol 157 43-48. 

The systems where this type of reaction is produced may be metal-, heme- or flavin-dependent. In flavin-dependent monooxygenases, a flavin-oxygen intermediate reacts with the substrate, producing water in a second step and requiring cofactors for regeneration of the flavin moiety. The non-heme-dependent oxygenases include the... 

Degradation of L-arginine by Streptomyces griseus is initiated by a hydroxylase that causes decarboxylation and conversion of the amino acid into an amide (Eq. 24-26), a reaction analogous to that catalyzed by the flavin-dependent lysine oxygenase (Eq. 18-41). The... 

Some bacteria, e.g., Pseudomonas putidap1 degrade L-lysine with a flavin-dependent oxygenase (Eq. 18-41) to 8-aminovaleramide ... 

Flavins are very versatile redox coenzymes. Flavopro-teins are dehydrogenases, oxidases, and oxygenases that catalyze a variety of reactions on an equal variety of substrate types. Since these classes of enzymes do not consist exclusively of flavoproteins, it is difficult to define catalytic specificity for flavins. Biological electron acceptors and donors in flavin-mediated reactions can be two-electron acceptors, such as NAD+ or NADP+, or a variety of one-electron acceptor systems, such as cytochromes (Fe2+/ Fe3+) and quinones, and molecular oxygen is an electron acceptor for flavoprotein oxidases as well as the source of oxygen for oxygenases. The only obviously common aspect of flavin-dependent reactions is that all are redox reactions. 

Biological oxidation of sulfides involves cytochromes P-450 or flavin-dependent oxygenases. A chiral flavin model was prepared by Shinkai etal. and used as the catalyst in the oxidation of aryl methyl sulfides [87]. Flavinophane 30 (Scheme 6C.10) is a compound with planar chirality. It catalyzes the oxidation of sulfides with 35% H202 in aqueous methanol at -20°C in the dark. 

W results not only from their redox-active ranging through oxidation states VI-IV, but because the intermediate V valence state is also accessible, they can act as interfaces between one- and two-electron redox systems, which allows them to catalyse hydroxylation of carbon atoms using water as the ultimate source of oxygen, (Figure 17.1) rather than molecular oxygen, as in the flavin-, haem- or Cu-dependent oxygenases, some of which we have encountered previously. For reviews see Hille, 2002 Brondino et al., 2006 Mendel and Bittner, 2006. 

The monooxygenase group of enzymes includes the non-P450 hydroxylases which catalyze the insertion of a hydroxyl group to replace a hydrogen atom at a saturated carbon [6-8] and the non-heme-dependent oxygenases such as the flavin-molybdenum-cobalt-dependent xanthine oxidase and aldehyde oxidase... 

NADPH oxidation and NO synthesis by the enzyme, it supports a role for reduction of the heme iron in catalysis, and may explain why NOS functions only as an NADPH-dependent reductase in the absence of bound calmodulin (Klatt et ai, 1993). The mechanism of calmodulin gating is envisioned to involve a conformational change between the reductase and oxygenase domains of NOS, such that an electron transfer between the terminal flavin and heme iron becomes possible. Calmodulin may also have a distinct role within the NOS reductase domain, in that its binding dramatically increases reductase activity of the enzyme toward cytochrome c (Klatt et al., 1993 Heinzel et al., 1992). However, it is clear that several other NOS functions occur independent of calmodulin, including the binding of L-arginine and NADPH, and transfer of NADPH-derived electrons into the flavins (Abu-Soud and Stuehr, 1993). 

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