The mtaA gene of the myxothiazol biosynthetic gene cluster from Stigmatella aurantiaca DW4/3-1 encodes a phosphopantetheinyl transferase that activates polyketide synthases and polypeptide synthetases

Myxothiazol is synthesized by the myxobacterium Stigmatella aurantiaca DW4/ 3-1 via a combined polyketide synthase/polypeptide synthetase, The biosynth esis of this secondary metabolite is also dependent on the gene product of mtaA. The deduced amino acid sequence of mtaA shows similarity to 4'-phosph opantetheinyl transferases (4'-PP transferase). This points to an enzyme ac tivity that converts inactive forms of the acyl carrier protein domains of polyketide synthetases (PKSs) and/or the peptidyl carrier protein domains o f nonribosomal polypeptide synthetases (NRPSs) of the myxothiazol synthetas e complex to their corresponding hole-forms. Heterologous co-expression of MtaA with an acyl carrier protein domain of the myxothiazol synthetase was performed in Escherichia coil, The proposed function as a 4'-PP transferase was confirmed and emphasizes the significance of MtaA for the formation of a catalytically active myxothiazol synthetase complex. Additionally, it is shown that MtaA has a relaxed substrate specificity: it processes an aryl carrier protein domain derived from the enterobactin synthetase off. coil ( ArCP) as well as a peptidyl carrier protein domain from a polypeptide synth etase of yet unknown function from Sorangium cellulosum. Therefore, MtaA sh ould be a useful tool for activating heterologously expressed PKS and NRPS systems.