CLONING AND NUCLEOTIDE-SEQUENCE OF THE PUTATIVE POLYKETIDE SYNTHASE GENES FOR PRADIMICIN BIOSYNTHESIS FROM ACTINOMADURA-HIBISCA

We cloned the putative polyketide synthase genes (pms genes) for pradi micin A biosynthesis from Actinomadura hibisca using an oligonucleotid e probe designed on the basis of conserved amino acid sequences of oth er polyketide synthases (PKSs). By DNA sequencing of an 8.2-kb SacI fr agment that hybridized with the oligonucleotide probe, 11 open reading frames (ORFs) were found. All of the ORFs except for ORF10 were predi cted to be translated in the same direction. Each of the deduced ORFs has significant sequence similarity to the protein responsible for pol yketide biosynthesis or spore pigmentation. In particular, ORF1, ORF2, and ORF3 were 50-70% identical with genes coding for PKSs for actinor hodin biosynthesis. Specific DNA regions similar in sequence to pms ge nes were found with genomic Southern hybridization in all of the pradi micin producers examined, but were not found in pradimicin nonproducer s, suggesting that the genes cloned in this study encode polyketide sy nthase for pradimicin biosynthesis.