The first gene in the biosynthesis of the polyketide antibiotic TA of Myxococcus xanthus codes for a unique PKS module coupled to a peptide synthetase

The polyketide antibiotic TA is synthesized by the Gram negative bacterium Myxococcus xanthus in a multi-step process in which a unique glycine-derive d molecule is used as a starter unit and elongated through the condensation of 11 acetate molecules by polyketide synthases (PKSs). Analysis of a 7.2 kb DNA fragment, encoding the protein that carries out the first condensati on step, revealed that the fragment constitutes a single open reading frame , referred to as Ta1, which lacks the 5' and 3' ends and displays two regio ns of similarity to other proteins. The first 1020 amino acid residues at t he N terminus of the polypeptide are similar to sequences of the large fami ly of enzymes encoding peptide synthetases. They are followed by a second r egion displaying a high degree of similarity to type I PKS genes. The genet ic analysis of this open reading frame is compatible with the proposed chem ical structure of TA. The data indicate that the genes encoding TA have a m odular gene organization, typical of a type I PKS system. The unusual featu re of Ta1 is that the first PKS module of TA resides on the same polypeptid e as the peptide synthetase functional unit. (C) 1999 Academic Press.