Distribution and functional analysis of the phosphopantetheinyl transferase superfamily in Actinomycetales microorganisms

Abstract

Phosphopantetheinyl transferases (PPTases) are a superfamily of essential enzymes required for the synthetic processes of many compounds including fatty acid, polyketide, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways via the transfer of a phosphopantetheinyl moiety to a serine residue in the conserved motif of carrier proteins. Since many Actinomycetales microorganisms produce a number of polyketide and nonribosomal peptide metabolites, the distribution of PPTase genes was investigated in these microorganisms. PPTases were found in bacterial protein databases using a hidden Markov model search with the PF01648 (4'-phosphopantetheinyl transferase superfamily) model. Actinomycetales microorganisms harbor several genes encoding AcpS-type and Sfp-type PPTases in individual genomes, many of which were associated with the biosynthetic gene cluster for polyketide or nonribosomal peptide metabolites. The properties of these PPTases were evaluated in the heterologous expression system using the biosynthetic gene clusters and genes encoding PPTases found in the present study. Sfp-type PPTases were classified into two subgroups, and although the substrate specificities of the enzymes in one subgroup were wide, the catalytic activities of enzymes in the other subgroup were low. SAV_1784 of Streptomyces avermitilis possessed the most characteristic broad-range activity against several type I polyketide synthases and nonribosomal peptide synthetases.