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An oxygenase that forms and deoxygenates toxic epoxide.

Catabolism may give rise to toxic intermediates that compromise cell vitality, such as epoxide formation in the recently elucidated and apparently universal bacterial coenzyme A (CoA)-dependent degradation of phenylacetic acid (1). This compound is central to the catabolism of a variety of aromatics... Full description

Journal Title: Nature March 7, 2012, Vol.483(7389), pp.359-362
Main Author: Teufel, Robin
Other Authors: Friedrich, Thorsten , Fuchs, Georg
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1476-4687 ; DOI: 10.1038/nature10862
Link: http://search.proquest.com/docview/928908915/?pq-origsite=primo
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recordid: proquest928908915
title: An oxygenase that forms and deoxygenates toxic epoxide.
format: Article
creator:
  • Teufel, Robin
  • Friedrich, Thorsten
  • Fuchs, Georg
subjects:
  • Biocatalysis–Chemistry
  • Epoxy Compounds–Metabolism
  • Iron–Toxicity
  • Molecular Sequence Data–Metabolism
  • Multienzyme Complexes–Chemistry
  • Oxygen–Genetics
  • Oxygenases–Metabolism
  • Phenylacetates–Chemistry
  • Pseudomonas–Metabolism
  • Thiolester Hydrolases–Chemistry
  • Thiolester Hydrolases–Genetics
  • Thiolester Hydrolases–Metabolism
  • Thiolester Hydrolases–Metabolism
  • Thiolester Hydrolases–Enzymology
  • Thiolester Hydrolases–Genetics
  • Thiolester Hydrolases–Metabolism
  • Epoxy Compounds
  • Multienzyme Complexes
  • Phenylacetates
  • Iron
  • Oxygenases
  • Thiolester Hydrolases
  • Phenylacetic Acid
  • Oxygen
ispartof: Nature, March 7, 2012, Vol.483(7389), pp.359-362
description: Catabolism may give rise to toxic intermediates that compromise cell vitality, such as epoxide formation in the recently elucidated and apparently universal bacterial coenzyme A (CoA)-dependent degradation of phenylacetic acid (1). This compound is central to the catabolism of a variety of aromatics, such as phenylalanine, lignin-related compounds or environmental contaminants (2,3). The key phenylacetyl-CoA monooxygenase (epoxidase) of the pathway, PaaABCE (1,4,5), is also connected to the production of various primary and secondary metabolites (6-9), as well as to the virulence of certain pathogens (1,10,11). However, the enzyme complex has so far not been investigated in detail. Here we characterize the bacterial multicomponent monooxygenase PaaABCE that, surprisingly, not only transforms phenylacetyl-CoA into its ring-1,2-epoxide, but also mediates the NADPH-dependent removal of the epoxide oxygen, regenerating phenylacetyl-CoA with formation of water. We provide evidence for a catalytic di-iron centre that is probably the key to the unprecedented deoxygenation of an organic compound by an oxygenase. Presumably, the bifunctionality is vital to avoid toxic intracellular epoxide levels if the subsequent catabolic steps are impeded. Our data suggest that detoxification is assisted by two thioesterases (Paal and PaaY) forming non-reactive breakdown products. Hence, PaaABCE may harbour an intrinsic escape mechanism from its own toxic product and represents the archetype of a bifunctional oxygenase/deoxygenase. Analogous reactions may possibly be catalysed by other di-iron epoxidases.
language: eng
source:
identifier: E-ISSN: 1476-4687 ; DOI: 10.1038/nature10862
fulltext: fulltext
issn:
  • 14764687
  • 1476-4687
url: Link


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titleAn oxygenase that forms and deoxygenates toxic epoxide.
creatorTeufel, Robin ; Friedrich, Thorsten ; Fuchs, Georg
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ispartofNature, March 7, 2012, Vol.483(7389), pp.359-362
identifierE-ISSN: 1476-4687 ; DOI: 10.1038/nature10862
subjectBiocatalysis–Chemistry ; Epoxy Compounds–Metabolism ; Iron–Toxicity ; Molecular Sequence Data–Metabolism ; Multienzyme Complexes–Chemistry ; Oxygen–Genetics ; Oxygenases–Metabolism ; Phenylacetates–Chemistry ; Pseudomonas–Metabolism ; Thiolester Hydrolases–Chemistry ; Thiolester Hydrolases–Genetics ; Thiolester Hydrolases–Metabolism ; Thiolester Hydrolases–Metabolism ; Thiolester Hydrolases–Enzymology ; Thiolester Hydrolases–Genetics ; Thiolester Hydrolases–Metabolism ; Epoxy Compounds ; Multienzyme Complexes ; Phenylacetates ; Iron ; Oxygenases ; Thiolester Hydrolases ; Phenylacetic Acid ; Oxygen
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descriptionCatabolism may give rise to toxic intermediates that compromise cell vitality, such as epoxide formation in the recently elucidated and apparently universal bacterial coenzyme A (CoA)-dependent degradation of phenylacetic acid (1). This compound is central to the catabolism of a variety of aromatics, such as phenylalanine, lignin-related compounds or environmental contaminants (2,3). The key phenylacetyl-CoA monooxygenase (epoxidase) of the pathway, PaaABCE (1,4,5), is also connected to the production of various primary and secondary metabolites (6-9), as well as to the virulence of certain pathogens (1,10,11). However, the enzyme complex has so far not been investigated in detail. Here we characterize the bacterial multicomponent monooxygenase PaaABCE that, surprisingly, not only transforms phenylacetyl-CoA into its ring-1,2-epoxide, but also mediates the NADPH-dependent removal of the epoxide oxygen, regenerating phenylacetyl-CoA with formation of water. We provide evidence for a catalytic di-iron centre that is probably the key to the unprecedented deoxygenation of an organic compound by an oxygenase. Presumably, the bifunctionality is vital to avoid toxic intracellular epoxide levels if the subsequent catabolic steps are impeded. Our data suggest that detoxification is assisted by two thioesterases (Paal and PaaY) forming non-reactive breakdown products. Hence, PaaABCE may harbour an intrinsic escape mechanism from its own toxic product and represents the archetype of a bifunctional oxygenase/deoxygenase. Analogous reactions may possibly be catalysed by other di-iron epoxidases.
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