A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate

Micah T. Nelp, Vahe Bandarian

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (preQ<inf>0</inf>). 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. Double duty: In bacterial and archeal biosynthesis of 7-deazpurines, a single enzyme, ToyM, catalyzes the two-step conversion of the carboxylic acid 7- carboxy-7-deazaguanine (CDG) into the corresponding nitrile, 7-cyano-7-deazaguanine (preQ<inf>0</inf>). The mechanism of this unusual direct transformation proceeds via the adenylation of CDG. This activates it to form the amide intermediate 7-amido-7-deazaguanine (ADG), which is in turn activated to form the nitrile.

Original languageEnglish (US)
Pages (from-to)10627-10629
Number of pages3
JournalAngewandte Chemie - International Edition
Volume54
Issue number36
DOIs
StatePublished - Sep 1 2015

Fingerprint

Nitriles
Carboxylic Acids
Carboxylic acids
Amides
Enzymes
Mathematical transformations
Biosynthesis
Adenosinetriphosphate
Catalysis
7-deazaguanine
Ligases
Acids
Substrates
Adenosine Triphosphate

Keywords

  • bioorganic chemistry
  • biosynthesis
  • enzymes
  • evolution
  • nitriles

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate. / Nelp, Micah T.; Bandarian, Vahe.

In: Angewandte Chemie - International Edition, Vol. 54, No. 36, 01.09.2015, p. 10627-10629.

Research output: Contribution to journalArticle

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