IDENTIFICATION AND CHARACTERIZATION OF THE NIDDAMYCIN POLYKETIDE SYNTHASE GENES FROM STREPTOMYCES CAELESTIS

The genes encoding the polyketide synthase (PKS) portion of the niddam ycin biosynthetic pathway were isolated from a library of Streptomyces caelestis NRRL-2821 chromosomal DNA. Analysis of 40 kb of DNA reveale d the presence of five large open reading frames (ORFs) encoding the s even modular sets of enzymatic activities required for the synthesis o f a 16-membered lactone ring. The enzymatic motifs identified within e ach module were consistent with those predicted from the structure of niddamycin. Disruption of the second ORF of the PKS coding region elim inated niddamycin production, demonstrating that the cloned genes are involved in the biosynthesis of this compound.