title: A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate.
abstract: The biosynthesis of nitriles is known to occur through specialized pathways involving multiple enzymes; however, in bacterial and archeal biosynthesis of 7-deazapurines, a single enzyme, ToyM, catalyzes the conversion of the carboxylic acid containing 7-carboxy-7-deazaguanine (CDG) into its corresponding nitrile, 7-cyano-7-deazaguanine (preQ0 ). The mechanism of this unusual direct transformation was shown to proceed via the adenylation of CDG, which activates it to form the newly discovered amide intermediate 7-amido-7-deazaguanine (ADG). This is subsequently dehydrated to form the nitrile in a process that consumes a second equivalent of ATP. The authentic amide intermediate is shown to be chemically and kinetically competent. The ability of ToyM to activate two different substrates, an acid and an amide, accounts for this unprecedented one-enzyme catalysis of nitrile synthesis, and the differential rates of these two half reactions suggest that this catalytic ability is derived from an amide synthetase that gained a new function.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1041 East Lowell Street, Biological Sciences West, Tucson, AZ 85721-0088 (USA).
authors.forename: Micah T
authors.initials: MT
authors.lastname: Nelp
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1041 East Lowell Street, Biological Sciences West, Tucson, AZ 85721-0088 (USA). vahe@email.arizona.edu.
authors.forename: Vahe
authors.initials: V
authors.lastname: Bandarian
mesh_terms: D000577:Amides / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D009570:Nitriles / Q000737:chemistry*
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D009570:Nitriles
keywords: bioorganic chemistry; biosynthesis; enzymes; evolution; nitriles