A NEW MYXOCOCCUS-XANTHUS GENE-CLUSTER FOR THE BIOSYNTHESIS OF THE ANTIBIOTIC SAFRAMYCIN MX1 ENCODING A PEPTIDE SYNTHETASE

The gene cluster for the biosynthesis of the heterocyclic quinone anti biotic saframycin Mx1 of Myxococcus xanthus DM504/15 was inactivated a nd tagged by Tn5 insertions. The tagged genes were cloned in Escherich ia coli and used to select overlapping cosmid clones spanning 58 kb of the M. xanthus genome. Gene disruption experiments defined a greater than or equal to 18 kb contiguous DNA region involved in saframycin bi osynthesis. Sequencing of part of this region revealed a large ORF con taining two 600-amino-acid domains with similarity to peptide syntheta se amino-acid-activating sequences, suggesting that saframycin Mx1 is synthesized by a nonribosomal multienzyme complex, similar to other bi oactive peptides.