MULTIENZYMATIC NON RIBOSOMAL PEPTIDE BIOSYNTHESIS - IDENTIFICATION OFTHE FUNCTIONAL DOMAINS CATALYZING PEPTIDE ELONGATION AND EPIMERIZATION

Peptide synthetases are multienzymatic complexes that synthesize bioac tive peptides molecules by the thiotemplate mechanism. Comparison of t he 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 sit e is nearly invariant. An identical motif is found in other enzymes ef fecting acyl transfer such as chloramphenicol acetyltransferase from T n9 and dihydrolipoamide acyltransferase. Altogether, the HHxxxDG motif may constitute the signature of a superfamily sharing a common cataly tic mechanism based on the acid-base properties of the second histidin e for effecting acyl transfer or peptide epimerisation.