Protein assembly line components in prodigiosin biosynthesis: characterization of PigA,G,H,I,J

J Am Chem Soc. 2006 Oct 4;128(39):12600-1. doi: 10.1021/ja063611l.


The red streptomycete metabolite prodigiosin has a unique tripyrrolic structure with two of the three pyrrolyl moieties in tandem. Five enzymes, PigA,G,H,I, and J, are involved in dipyrrole (rings A and B) formation. We have heterologously expressed and purified from Escherichia coli these five enzymes. At first, pyrrole ring A is formed on the peptidyl carrier protein PigG by one of two possible ways: (i) by action of the adenylation domain PigI that transforms l-proline into l-prolyl-AMP and by the flavoprotein dehydrogenase PigA responsible for the four-electron oxidation reaction; (ii) by loading with the pyrrolyl-2-carboxyl-(S)-pantetheinyl moiety from synthetic pyrrolyl-CoA using the phosphopantetheinyl transferase Sfp. Subsequently, pyrrole ring B is constructed by PigH after the transfer of ring A to the ketosynthase of PigJ. PigH consists of three domains: two acyl carrier proteins (ACPs) and a seryltransferase (SerT). Using HPLC and nanospray-Fourier Transform Mass Spectrometry (nFTMS), we established that all three domains of PigH undergo post-translational modifications and gained insight into the machinery involved in 2,2-dipyrrole biosynthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Mass Spectrometry
  • Phenylpropionates
  • Prodigiosin / biosynthesis*
  • Proline / metabolism
  • Pyrroles / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serratia / enzymology*
  • Serratia / metabolism


  • Carrier Proteins
  • Phenylpropionates
  • Pyrroles
  • Recombinant Proteins
  • 4-hydroxyphenyllactic acid
  • Proline
  • Prodigiosin