2 MULTIFUNCTIONAL PEPTIDE SYNTHETASES AND AN O-METHYLTRANSFERASE ARE INVOLVED IN THE BIOSYNTHESIS OF THE DNA-BINDING ANTIBIOTIC AND ANTITUMOR AGENT SAFRAMYCIN MX1 FROM MYXOCOCCUS-XANTHUS
A. Pospiech et al., 2 MULTIFUNCTIONAL PEPTIDE SYNTHETASES AND AN O-METHYLTRANSFERASE ARE INVOLVED IN THE BIOSYNTHESIS OF THE DNA-BINDING ANTIBIOTIC AND ANTITUMOR AGENT SAFRAMYCIN MX1 FROM MYXOCOCCUS-XANTHUS, Microbiology, 142, 1996, pp. 741-746
Saframycin Mx1 is a DNA-binding antibiotic and antitumour agent produc
ed by Myxococcus xanthus. It is a heterocyclic quinone, thought to be
synthesized via the linear pepide intermediate AlaGlyTyrTyr. Analysis
of 14.1 kb DNA sequence involved in saframycin production revealed gen
es for two large multifunctional peptide synthetases of 1770 and 2605
amino acids, respectively, and a putative O-methyltransferase of 220 a
mino acids. The three ORFs read in the same direction and are separate
d by short non-translated gaps of 44 and 49 bp. The peptide synthetase
s contain two amino-acid-activating domains each. The first domain lac
ks two of the most conserved 'core' sequences, and the last domain is
followed by a putative reductase functionality, not previously seen in
peptide synthetases. Complementation tests showed that antibiotic-non
producing mutant strains lacking one of the peptide synthetases secret
e a substrate, presumably a modified amino acid precursor, that can be
used by O-methyltransferase-deficient mutant strains to synthesise sa
framycin Mx1.