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). 

Scheme 10.17 Reaction cycle of the flavin-dependent squalene monooxygenase. Dashed arrows indicate electron transport.

Like the examples above, dihydroxyacetanilide epoxidase (DHAE) uses an olefin as the substrate for epoxidation. Its mechanism, however, is fundamentally different from those of cytochrome P450 or flavin-dependent enzymes. Dihydroxyacetanilide is an intermediate in the biosynthesis of the epoxyquinones LL-C10037a, an antitumor agent produced by the actinomycete Streptomyces LL-C10037 [75, 76], and MM14201, an antibiotic produced by Streptomyces MPP 3051 (Scheme 10.20) [77]. The main structural difference between the two antibiotics lies in the opposite stereochemistry of the oxirane ring. 

Enzyme-mediated chiral sulfoxidation has been reviewed comprehensively in historical context [188-191]. The biotransformation can be mediated by cytochrome P-450 and flavin-dependent MOs, peroxidases, and haloperoxidases. Owing to limited stability and troublesome protein isolation, a majority of biotransformations were reported using whole-cells or crude preparations. In particular, fungi have been identified as valuable sources of such biocatalysts and the catalytic entities have not been fully identified in all cases. 

An advanced technique for the clean generation of (25) in situ is based on the oxidation of i-glycerol 3-phosphate (35) catalyzed by microbial flavine-dependent glycerol phosphate oxidases (GPO) (Figure 10.19, box) [102]. This method generates... 

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). 

Yang W, IF Moore, KP Koteva, DC Bareich, DW Hughe, GD Wright (2004) TetX is a flavin-dependent monooxygenase conferring resiatence to tetracycline antibiotics. J Biol Chem 279 52346-52352. 

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. 

Hartmann S, C Hultschig, W Eisenreich, G Fuchs, A Bacher, S Ghisla (1999) NIH shift in flavin-dependent monooxygenation mechanistic studies with 2-aminobenzoyl-CoA monooxygenase/reductase. Proc Natl Acad USA 96 7831-7836. 

Becker D, T Schrader, JR Andreesen (1997) Two-component flavin-dependent pyrrole-2-carboxylate monooxygenase from Rhodococcus sp. Eur J Biochem 249 739-747. 

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... 

Reduced flavins (FADH2, FMNH2, and riboflavin) generated by flavin-dependent reductases have been hypothesized to reduce azo dyes in a nonspecific chemical reaction, and flavin reductases have been revealed to be indeed anaerobic azoreductases. Other reduced enzyme cofactors, for example, NADH, NADH, NADPH, and an NADPH-generating system, have also been reported to reduce azo dyes. Except for enzyme cofactors, different artificial redox mediating compounds, especially such as quinines, are important redox mediators of azo dye anaerobic reduction (Table 1). 

From the biological point of view, the effect of anaerobiosis has been characterized in purely anaerobic, facultative anaerobic, and aerobic bacteria, in yeasts, and in tissues from higher organisms [6-12], From these studies it can be deduced that almost every azo compound can be biologically reduced under anaerobic conditions [4]. Reduced flavins are produced by cytosol flavin-dependent reductases [6, 13], while quinone reductase activity located in the plasma membrane [14] and extracellular azo reductase activities [9, 15] were also observed. 

In contrast to the flavin-dependent monoamine oxidases, SSAO/VAP-1 has evolved to hydroxylate a tyrosine residue in the active site which is further oxidized to the quinone state by oxygen in the presence of copper ion releasing hydrogen peroxide [28-30]. The primary amine in the substrate (R-NH2, Scheme 1) forms a Schiff-base with the quinone carbonyl group, which through a series of steps ultimately releases the aldehyde product. 

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