Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway

Chem Biol. 2005 Jun;12(6):665-75. doi: 10.1016/j.chembiol.2005.04.010.


Butirosins A and B are naturally occurring aminoglycoside antibiotics that have a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. Semisynthetic addition of AHBA to clinically valuable aminoglycoside antibiotics has been shown both to improve their pharmacological properties and to prevent their deactivation by a number of aminoglycoside-modifying enzymes involved in bacterial resistance. We report here that the biosynthesis of AHBA from L-glutamate, encoded within a previously identified butirosin biosynthetic gene cluster, proceeds via intermediates tethered to a specific acyl carrier protein (ACP). Five components of the pathway have been purified and characterized, including the ACP (BtrI), an ATP-dependent ligase (BtrJ), a pyridoxal phosphate-dependent decarboxylase (BtrK), and a two-component flavin-dependent monooxygenase system (BtrO and the previously unreported BtrV). The proposed biosynthetic pathway includes a gamma-glutamylation of an ACP-derived gamma-aminobutyrate intermediate, possibly a rare example of protective group chemistry in biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / metabolism*
  • Acylation
  • Amino Acids / chemistry
  • Amino Acids / metabolism*
  • Aminobutyrates / chemistry
  • Aminobutyrates / metabolism
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Bacillus / chemistry
  • Bacillus / metabolism
  • Butirosin Sulfate / biosynthesis*
  • Butirosin Sulfate / chemistry*
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Hydroxylation
  • Molecular Structure
  • Multigene Family


  • Acyl Carrier Protein
  • Amino Acids
  • Aminobutyrates
  • Anti-Bacterial Agents
  • 2,4-diaminobutyric acid
  • Glutamic Acid
  • Butirosin Sulfate