Characterization of a new tailoring domain in polyketide biogenesis: the amine transferase domain of MycA in the mycosubtilin gene cluster

J Am Chem Soc. 2005 Nov 2;127(43):14986-7. doi: 10.1021/ja055247g.

Abstract

We report the expression and characterization of a truncated form of MycA from the Mycosubtilin gene cluster from Bacillus subtilis. The MycA fragment contains a new amino transferase (AMT) tailoring domain, allowing the first detailed study of a PLP-dependent enzyme operating in cis within the PKS and NRPS biosynthetic paradigm. As the AMT domain acts on covalently bound beta-ketothioesters, and is therefore a single-turnover system, electrospray ionization-Fourier transform mass spectrometry (ESI-FTMS) was used to observe the amine-transfer reaction both for amine donor substrate specificity and to regiospecifically determine enzyme-bound intermediates. We confirm the function of the AMT domain, dissect the mechanistic steps of amine transfer, identify the preferred amine source, and localize the beta-ketothioester substrate during amine transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacillus subtilis / enzymology
  • Lipoproteins / biosynthesis
  • Lipoproteins / genetics
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Multigene Family*
  • Polyketide Synthases / chemistry
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transaminases / chemistry
  • Transaminases / genetics
  • Transaminases / metabolism*

Substances

  • Lipoproteins
  • Multienzyme Complexes
  • mycosubtiline
  • Polyketide Synthases
  • Transaminases