Oxidation of amines by flavoproteins

Fitzpatrick, Paul F.

doi:10.1016/j.abb.2009.07.019

Cited by 189 publications

(184 citation statements)

References 133 publications

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“…For this reason, the other copper-dependent enzymes of the cell are either localized here (the multicopper oxidase and copper/zinc superoxide dismutase) or loaded with copper from here (the cytochrome bo oxidase). However, flavin-dependent MAOs are common in nature (55), so a simpler arrangement would be for E. coli to rely upon a cytoplasmic flavin MAO. Because flavins are not exported to the periplasm, it is more likely that the periplasmic localization of the E. coli MAO is the basis for its utilization of topaquinone and copper rather than vice versa.…”

Section: Discussionmentioning

confidence: 99%

How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway

Kumar

Imlay

2013

J Bacteriol

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When Escherichia coli grows on conventional substrates, it continuously generates 10 to 15 M/s intracellular H 2 O 2 through the accidental autoxidation of redox enzymes. Dosimetric analyses indicate that scavenging enzymes barely keep this H 2 O 2 below toxic levels. Therefore, it seemed potentially problematic that E. coli can synthesize a catabolic phenylethylamine oxidase that stoichiometrically generates H 2 O 2 . This study was undertaken to understand how E. coli tolerates the oxidative stress that must ensue. Measurements indicated that phenylethylamine-fed cells generate H 2 O 2 at 30 times the rate of glucose-fed cells. Two tolerance mechanisms were identified. First, in enclosed laboratory cultures, growth on phenylethylamine triggered induction of the OxyR H 2 O 2 stress response. Null mutants (⌬oxyR) that could not induce that response were unable to grow. This is the first demonstration that OxyR plays a role in protecting cells against endogenous H 2 O 2 . The critical element of the OxyR response was the induction of H 2 O 2 scavenging enzymes, since mutants that lacked NADH peroxidase (Ahp) grew poorly, and those that additionally lacked catalase did not grow at all. Other OxyR-controlled genes were expendable. Second, phenylethylamine oxidase is an unusual catabolic enzyme in that it is localized in the periplasm. Calculations showed that when cells grow in an open environment, virtually all of the oxidase-generated H 2 O 2 will diffuse across the outer membrane and be lost to the external world, rather than enter the cytoplasm where H 2 O 2 -sensitive enzymes are located. In this respect, the periplasmic compartmentalization of phenylethylamine oxidase serves the same purpose as the peroxisomal compartmentalization of oxidases in eukaryotic cells.

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Section: Discussionmentioning

confidence: 99%

How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway

Kumar

Imlay

2013

J Bacteriol

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“…4 In addition, the ability of flavoproteins to oxidize amines to imines has been exploited for the synthesis of chiral amines (Scheme 1). 5 Initial experiments by Hafner and Weller 6 using D-amino acid oxidase in combination with sodium borohydride led to the preparation of L-amino acids from the corresponding R-enantiomers. Applying the same concept, Soda and co-workers 7 demonstrated the deracemization of racemic amino acids.…”

Section: Introductionmentioning

confidence: 99%

Cyclohexylamine oxidase as a useful biocatalyst for the kinetic resolution and dereacemization of amines

et al. 2012

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Abstract:The biocatalytic performance of a cloned cyclohexylamine oxidase derived from Brevibacterium oxydans IH-35A towards structurally different amines was investigated. Cycloalkyl primary amines, alkyl aryl amines, and a-carbon-substituted aliphatic amines were identified as suitable substrates for the biocatalyst based on an activity assay. Kinetic resolutions of several amines by either recombinant whole cells or crude enzyme extracts prepared therefrom gave enantiomerically pure (R)-amines besides the corresponding ketones. When cyclohexylamine oxidase in combination with a boraneammonia complex as reducing agent was applied to the deracemization of several substrates, excellent enantiomeric ratios (>99:1) and good isolated yields (62%-75%) of the corresponding (R)-amines were obtained.Key words: biocatalysis, cyclohexylamine oxidase, chiral amines, kinetic resolution, deracemization.Résumé : On a étudié la performance biocatalytique d'un clone de l'oxydase de la cyclohexylamine dérivé du Brevibacterium oxydans IH-35A vis-à-vis des amines de structures diverses. Sur la base d'un essai d'activité, il a été possible d'identifier les cycloalkylamines primaires, les alkylarylamines primaires et les amines aliphatiques portant un substituant sur le carbone en a comme des substrats appropriés pour le biocatalyseur. Les résolutions cinétiques de plusieurs amines par des cellules recombinantes complètes ou des extraits bruts d'enzyme préparés à partir de celles-ci conduisent à des amines (R) énantiomériquement pures aux côtés des cétones correspondantes. On a utilisé l'oxydase de la cyclohexylamine en combinaison avec un complexe de borane-ammoniac comme agent réducteur pour effectuer la déracémisation de plusieurs substrats, avec d'excellents rapports énantiomériques (>99/1) et de bons rendements en produits isolés (72 % à 75 %) des amines (R) correspondantes.

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“…The oxidases of this superfamily belong either to the L-amino acid oxidase or to the D-amino acid oxidase structural families, renalase more closely resembling the former enzymes, which encompass also MAOs. In comparison to most of its structural homologs, renalase lacks a third domain, which in PHBH is named the interface domain [50], and which participates in substrate binding in MAOs and polyamine oxidase [51]. Due to the absence of this structural element, the polar, positively charged cavity of 224 Å 3 that faces the re side of the flavin ring and presumably represents the active site is freely accessible to the solvent trough a large opening [20].…”

Section: Nadph-dependent Diaphorase Reactions With Various Artificialmentioning

confidence: 99%

Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme

Baroni¹,

Milani²,

Pandini³

et al. 2013

CPD

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Renalase is a flavoprotein recently discovered in humans, preferentially expressed in the proximal tubules of the kidney and secreted in blood and urine. It is highly conserved in vertebrates, with homologs identified in eukaryotic and prokaryotic organisms. Several genetic, epidemiological, clinical and experimental studies show that renalase plays a role in the modulation of the functions of the cardiovascular system, being particularly active in decreasing the catecholaminergic tone, in lowering blood pressure and in exerting a protective action against myocardial ischemic damage. Deficient renalase synthesis might be the cause of the high occurrence of hypertension and adverse cardiac events in kidney disease patients. Very recently, recombinant human renalase has been structurally and functionally characterized in vitro. Results show that it belongs to the p-hydroxybenzoate hydroxylase structural family of flavoenzymes, contains non-covalently bound FAD with redox features suggestive of a dehydrogenase activity, and is not a catecholamine-degrading enzyme, either through oxidase or NAD(P)H-dependent monooxygenase reactions. The biochemical data now available will hopefully provide the basis for a systematic and rational quest toward the identification of the reaction catalyzed by renalase and of the molecular mechanism of its physiological action, which in turn are expected to favor the development of novel therapeutic tools for the treatment of kidney and cardiovascular diseases.

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Oxidation of amines by flavoproteins

Cited by 189 publications

References 133 publications

How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway

How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway

Cyclohexylamine oxidase as a useful biocatalyst for the kinetic resolution and dereacemization of amines

Is Renalase a Novel Player in Catecholaminergic Signaling? The Mystery of the Catalytic Activity of an Intriguing New Flavoenzyme

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