The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin - A New polyketide synthase organization encoded by two subclusters separated by functionalization genes

The biosynthetic gene cluster for the 26-membered ring of the polyene macro lide pimaricin extends for about 110 kilobase pairs of contiguous DNA in th e genome of Streptomyces natalensis, Two sets of polyketide synthase (PKS) genes are separated by a group of small polyketide-functionalizing genes. T wo of the polyketide synthase genes, pimS0 and pimS1, have been fully seque nced and disrupted proving the involvement of each of these genes in pimari cin biosynthesis, The pimS0 gene encodes a relatively small acetate-activat ing PKS (similar to 193 kDa) that appears to work as a loading protein whic h "presents" the starter unit to the second PKS subunit. The pimS1 gene enc odes a giant multienzyme (similar to 710 kDa) harboring 15 activities respo nsible for the first four cycles of chain elongation in pimaricin biosynthe sis, resulting in formation of the polyene chromophore.