Multienzymatic non ribosomal peptide biosynthesis: identification of the functional domains catalysing peptide elongation and epimerisation.
Peptide synthetases are multienzymatic complexes that synthesize bioactive peptides molecules by the thiotemplate mechanism. Comparison of the known sequences of peptide synthetases led us to the identification of a 350 amino acids domain catalysing elongation and containing the motif HHxxxDG. This motif is present as many times as acyltransfer or epimerisation reactions occur during biosynthesis of the peptide. The distance between this motif and the phosphopantetheinyl attachment site is nearly invariant. An identical motif is found in other enzymes effecting acyl transfer such as chloramphenicol acetyltransferase from Tn9 and dihydrolipoamide acyltransferase. Altogether, the HHxxxDG motif may constitute the signature of a superfamily sharing a common catalytic mechanism based on the acid-base properties of the second histidine for effecting acyl transfer or peptide epimerisation.
Unité de biochimie microbienne, URA 1300 CNRS, Institut Pasteur, Paris, France.
V
V
De Crécy-Lagard
P
P
Marlière
W
W
Saurin
D000217:Acyltransferases / Q000737:chemistry; D000595:Amino Acid Sequence; D002384:Catalysis; D015500:Chloramphenicol O-Acetyltransferase / Q000737:chemistry; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism
D000217:Acyltransferases; C033588:dihydrolipoamide acyltransferase; D015500:Chloramphenicol O-Acetyltransferase; D010453:Peptide Synthases