Catalysis of a flavoenzyme-mediated amide hydrolysis.
A new pyrimidine catabolic pathway (the Rut pathway) was recently discovered in Escherichia coli K12. In this pathway, uracil is converted to 3-hydroxypropionate, ammonia, and carbon dioxide. The seven-gene Rut operon is required for this conversion. Here we demonstrate that the flavoenzyme RutA catalyzes the initial uracil ring-opening reaction to give 3-ureidoacrylate. This reaction, while formally a hydrolysis reaction, proceeds by an oxidative mechanism initiated by the addition of a flavin hydroperoxide to the C4 carbonyl. While peroxide-catalyzed amide hydrolysis has chemical precedent, we are not aware of a prior example of analogous chemistry catalyzed by flavin hydroperoxides. This study further illustrates the extraordinary catalytic versatility of the flavin cofactor.
Mukherjee
Tathagata
T
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Zhang
Yang
Y
Abdelwahed
Sameh
S
Ealick
Steven E
SE
Begley
Tadhg P
TP
D000179:Acrylates / Q000737:chemistry / Q000378:metabolism; D000577:Amides / Q000378:metabolism*; D055162:Biocatalysis; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D006868:Hydrolysis; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D011487:Protein Conformation
D000179:Acrylates; D000577:Amides; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases; C036658:acrylic acid