CLONING AND CHARACTERIZATION OF A POLYKETIDE SYNTHASE GENE FROM STREPTOMYCES-FRADIAE TU2717, WHICH CARRIES THE GENES FOR BIOSYNTHESIS OF THE ANGUCYCLINE ANTIBIOTIC URDAMYCIN-A AND A GENE PROBABLY INVOLVED IN ITS OXYGENATION

A DNA fragment was cloned as cosmid purd8, which encodes a polyketide synthase invoiced in the production of the angucycline antibiotic urda mycin from Streptomyces fradiae Tu2717. Deletion of the polyketide syn thase genes from the chromosome abolished urdamycin production, In add ition, purd8 conferred urdamycin resistance on introduction into Strep tomyces lividans TK24. Sequence analysis of 5.7 kb of purd8 revealed s ix open reading frames transcribed in the same direction, The deduced amino acid sequences of the sis open reading frames strongly resemble proteins from known type II polyketide synthase gene clusters: a ketoa cyl synthase, a chain length factor, an acyl carrier protein, a ketore ductase, a cyclase, and an oxygenase. Heterologous expression of the u rdamycin genes encoding a ketoacyl synthase and a chain length factor in Streptomyces glaucescens tetracenomycin C-nonproducing mutants impa ired in either the TcmK ketoacyl synthase or TcmL chain length factor resulted in the production of tetracenomycin C. Heterologous expressio n of a putative oxygenase gene from the urdamycin gene cluster in S, g laucescens GLA.O caused production of the hybrid antibiotic 6-hydroxy tetracenomycin C.