Hexachlorobenzene Catabolism Involves a Nucleophilic Aromatic Substitution and Flavin-N5-Oxide Formation.

HcbA1 is a unique flavoenzyme that catalyzes the first step in the bacterial hexachlorobenzene catabolic pathway. Here we report in vitro reconstitution of the HcbA1-catalyzed reaction. Detailed mechanistic studies provide evidence for nucleophilic aromatic substitution and flavin-N5-oxide formation.

[1]  R. Teufel,et al.  Insights into the enzymatic formation, chemical features, and biological role of the flavin-N5-oxide. , 2018, Current opinion in chemical biology.

[2]  B. Moore,et al.  Enzymatic control of dioxygen binding and functionalization of the flavin cofactor , 2018, Proceedings of the National Academy of Sciences.

[3]  R. Teufel Preparation and Characterization of the Favorskiiase Flavoprotein EncM and Its Distinctive Flavin-N5-Oxide Cofactor. , 2018, Methods in enzymology.

[4]  R. Teufel Flavin-catalyzed redox tailoring reactions in natural product biosynthesis. , 2017, Archives of biochemistry and biophysics.

[5]  T. Begley,et al.  Flavin-N5-oxide: A new, catalytic motif in flavoenzymology. , 2017, Archives of biochemistry and biophysics.

[6]  T. Begley,et al.  RutA-Catalyzed Oxidative Cleavage of the Uracil Amide Involves Formation of a Flavin-N5-oxide. , 2017, Biochemistry.

[7]  B. Moore,et al.  Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse. , 2017, Chemical reviews.

[8]  T. Begley,et al.  Dibenzothiophene Catabolism Proceeds via a Flavin-N5-oxide Intermediate. , 2016, Journal of the American Chemical Society.

[9]  B. Moore,et al.  Unusual flavoenzyme catalysis in marine bacteria. , 2016, Current opinion in chemical biology.

[10]  P. Dorrestein,et al.  Biochemical Establishment and Characterization of EncM's Flavin-N5-oxide Cofactor. , 2015, Journal of the American Chemical Society.

[11]  B. Moore,et al.  Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement , 2013, Nature.

[12]  S. Copley,et al.  Sequestration of a highly reactive intermediate in an evolving pathway for degradation of pentachlorophenol , 2013, Proceedings of the National Academy of Sciences.

[13]  S. Copley,et al.  Pentachlorophenol hydroxylase, a poorly functioning enzyme required for degradation of pentachlorophenol by Sphingobium chlorophenolicum. , 2012, Biochemistry.

[14]  P. Karplus,et al.  Typical 2‐Cys peroxiredoxins – structures, mechanisms and functions , 2009, The FEBS journal.

[15]  J. Strap,et al.  The recent evolution of pentachlorophenol (PCP)-4-monooxygenase (PcpB) and associated pathways for bacterial degradation of PCP , 2007, Biodegradation.

[16]  K. Jones,et al.  Hexachlorobenzene in the global environment: emissions, levels, distribution, trends and processes. , 2005, The Science of the total environment.

[17]  B. Dijkstra,et al.  Structure and mechanism of bacterial dehalogenases: different ways to cleave a carbon-halogen bond. , 2003, Current opinion in structural biology.

[18]  D. Dunaway-Mariano,et al.  Raman evidence for Meisenheimer complex formation in the hydrolysis reactions of 4-fluorobenzoyl- and 4-nitrobenzoyl-coenzyme A catalyzed by 4-chlorobenzoyl-coenzyme A dehalogenase. , 2002, Biochemistry.

[19]  D. Dunaway-Mariano,et al.  Role of active site binding interactions in 4-chlorobenzoyl-coenzyme A dehalogenase catalysis. , 2001, Biochemistry.

[20]  Histidine 90 function in 4-chlorobenzoyl-coenzyme a dehalogenase catalysis. , 2001, Biochemistry.

[21]  E. Lau,et al.  The active site dynamics of 4-chlorobenzoyl-CoA dehalogenase , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Fetzner Bacterial dehalogenation , 1998, Applied Microbiology and Biotechnology.

[23]  D. Dunaway-Mariano,et al.  Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation. , 1996, Biochemistry.