A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase

Abstract

The gene cluster for the biosynthesis of the heterocyclic quinone antibiotic saframycin Mx1 of Myxococcus xanthus DM504/15 was inactivated and tagged by Tn5 insertions. The tagged genes were cloned in Escherichia coli and used to select overlapping cosmid clones spanning 58 kb of the M. xanthus genome. Gene disruption experiments defined a > or = 18 kb contiguous DNA region involved in saframycin biosynthesis. Sequencing of part of this region revealed a large ORF containing two 600-amino-acid domains with similarity to peptide synthetase amino-acid-activating sequences, suggesting that saframycin Mx1 is synthesized by a nonribosomal multienzyme complex, similar to other bioactive peptides.