Flavin oxidoreductases

There is some evidence that the iron-sulfur protein, FhuF, participates in the mobilization of iron from hydroxamate siderophores in E. coli (Muller et ah, 1998 Hantke, K. unpublished observations). However, a reductase activity of FhuF has not been demonstrated. Many siderophore-iron reductases have been shown to be active in vitro and some have been purified. The characterization of these reductases has revealed them to be flavin reductases which obtain the electrons for flavin reduction from NAD(P)H, and whose main functions are in areas other than reduction of ferric iron (e.g. flavin reductase Fre, sulfite reductase). To date, no specialized siderophore-iron reductases have been identified. It has been suggested that the reduced flavins from flavin oxidoreductases are the electron donors for ferric iron reduction (Fontecave et ah, 1994). Recently it has been shown, after a fruitless search for a reducing enzyme, that reduction of Co3+ in cobalamin is achieved by reduced flavin. Also in this case it was suggested that cobalamins and corrinoids are reduced in vivo by flavins which may be generated by the flavin... 

The Keasling group [175] demonstrated that the flavin reductase from Vibrio harveyi, when expressed in E. coli along with the dsz cassette, enhanced biodesulfurization rate by about six-fold. However, it should be noted that the overexpression of the flavin oxidoreductase results only in increase in DBT removal rate, but not HBP production rate. This is expected since the flavin reductase is only required for the first two steps of desulfurization. Another interesting result from this study was the reduced rate of HBP production when the flavin reductase was co-expressed. This was probably due... 

Ishii, Y. Ohshiro, T. Aoi, Y., et al., Identification of the Gene Encoding a NAD(P)H-Flavin Oxidoreductase Coupling With Dibenzothiophene (DBT)-Desulfurizing Enzymes From the DBT-Nondesulfurizing Bacterium Paenibacillus Polymyxa A-l. Journal of Bioscience and Bioengineering, 2000. 90(2) pp. 220-222. 

Dehydrogenases (SH2— S + 2e + 2H+) NADH/flavin oxidoreductase N-methylglutamate synthetase... 

Eranklund, C. E., Baron, S. E., and Hylemon, P. B., 1993, Characterisation of the bai H gene encoding a bile acid-inducible NADH flavin oxidoreductase from Eubacterium sp. VPI 12708, J. Bacterial. 175 300293012. 

Louie TM, Xie XS, Xun L. Coordinated production and utilization of FADH2 by NAD(P)H-flavin oxidoreductase and 4-hydroxy-phenylacetate 3-monooxygenase. Biochemistry 2003,42 7509 -7517. 

An NADH-flavin oxidoreductase was also induced by cholic acid in this bacterium [61]. The physiological function of this enzyme in 7-dehydroxylation is presently unknown. Moreover, it is not known which of the induced polypeptides constitute 7-dehydroxylase however, the polypeptides of 56 000 and 27 000 molecular weight co-purify with enzymatic activity upon anaerobic high-performance gel filtration. 

The cDNA and corresponding primary amino acid sequences of several CPRs including rat , rabbit- , and human were obtained by the mid-1980s, and the development of Escherichia coli expression systems paved the way for detailed molecular characterization of the polypeptide through site-directed mutagenesis. The three-dimensional structure of rat CPR was determined by X-ray crystallography in 1997 by Kim and coworkers -, providing the structural prototype for dual flavin oxidoreductases. 

Enzyme sensors for carbohydrates. An enzyme electrode for glucose was the first electrochemical biosensor studied [1] and since then intensive research has taken place, providing new ideas and experiences for the development of other biosensors. Glucose biosensors usually use as a biological component the relatively stable enzyme glucose oxidase, preferably from Aspergillus niger (Fig. 14). This enzyme may serve as a model for all flavin oxidoreductases which can be applied not only for... 

Besides flavin oxidoreductases the appropriate dehydrogenase systems could also be used for assaying sugars and other dehydrogenase substrates (e.g., ethanol, lactate, and amino acids). In contrast to FAD,... 

Fontecave M, Ehasson R, Reichard P. 1987. NAD(P)H-flavin oxidoreductase of Escherichia coli a ferric iron reductase participating in the generation of the free-radical ofribonucleotide reductase. J Rio/ Chem 262 12325—12331. 

However, the most extensively investigated class of ERs is members of the OYE family of flavin oxidoreductases (EC 1.6.99.1). There is detailed information known about OYEs, such as their structure, reaction mechanism, substrate scope, kinetic properties, and biocatalytic approaches. Therefore, this chapter will focus on this latter class of enzymes. They have been intensively studied over the past decade in view of their applicability in preparative-scale biotransformations [1, 8-12]. These FMN-containing enzymes catalyze the asymmetric reduction of a,p-unsaturated... 

ELAVOPROTEINS. Flavin is an essential substance for the activity of a number of important oxidoreductases. We discuss the chemistry of flavin and its derivatives, FMN and FAD, in the chapter on electron transport and oxidative phosphorylation (Chapter 21). 

Puget, K., and Michelson, A. M. (1972). Studies in bioluminescence. VII Bacterial NADH flavine mononucleotide oxidoreductase. Biochimie 54 1197-1204. 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Further improvements can be achieved by replacing the oxygen with a non-physiological (synthetic) electron acceptor, which is able to shuttle electrons from the flavin redox center of the enzyme to the surface of the working electrode. Glucose oxidase (and other oxidoreductase enzymes) do not directly transfer electrons to conventional electrodes because their redox center is surroimded by a thick protein layer. This insulating shell introduces a spatial separation of the electron donor-acceptor pair, and hence an intrinsic barrier to direct electron transfer, in accordance with the distance dependence of the electron transfer rate (11) ... 

Gisi MR, L Xun (2003) Characterization of chlorophenol 4-monooxygenase (TftD) and NADH flavin adenine dinucleotide oxidoreductase (TftC) of Burkholderia cepacia ACllOO. J Bacteriol 185 2786-2792. 

Upon purification of the XDH from C. purinolyticum, a separate Se-labeled peak appeared eluting from a DEAE sepharose column. This second peak also appeared to contain a flavin based on UV-visible spectrum. This peak did not use xanthine as a substrate for the reduction of artificial electron acceptors (2,6 dichlor-oindophenol, DCIP), and based on this altered specificity this fraction was further studied. Subsequent purification and analysis showed the enzyme complex consisted of four subunits, and contained molybdenum, iron selenium, and FAD. The most unique property of this enzyme lies in its substrate specificity. Purine, hypoxanthine (6-OH purine), and 2-OH purine were all found to serve as reductants in the presence of DCIP, yet xanthine was not a substrate at any concentration tested. The enzyme was named purine hydroxylase to differentiate it from similar enzymes that use xanthine as a substrate. To date, this is the only enzyme in the molybdenum hydroxylase family (including aldehyde oxidoreductases) that does not hydroxylate the 8-position of the purine ring. This unique substrate specificity, coupled with the studies of Andreesen on purine fermentation pathways, suggests that xanthine is the key intermediate that is broken down in a selenium-dependent purine fermentation pathway. ... 

Riboflavin (from the Latin flavus, yellow) serves in the metabolism as a component of the redox coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD see p. 104). As prosthetic groups, FMN and FAD are cofactors for various oxidoreductases (see p. 32). No specific disease due to a deficiency of this vitamin is known. 

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