Wide Distribution of Foxicin Biosynthetic Gene Clusters in Strains - An Unusual Secondary Metabolite with Various Properties.

Tü6028 is known to produce the polyketide antibiotic polyketomycin. The deletion of the oxygenase gene led to a non-polyketomycin-producing mutant. Instead, novel compounds were produced by the mutant, which have not been detected before in the wild type strain. Four different compounds were identified and named foxicins A-D. Foxicin A was isolated and its structure was elucidated as an unusual nitrogen-containing quinone derivative using various spectroscopic methods. Through genome mining, the foxicin biosynthetic gene cluster was identified in the draft genome sequence of . The cluster spans 57 kb and encodes three PKS type I modules, one NRPS module and 41 additional enzymes. A gene-inactivated mutant of Tü6028 Δ is unable to produce foxicins. Homologous biosynthetic gene clusters were found in more than 20 additional strains, overall in about 2.6% of all sequenced genomes. However, the production of foxicin-like compounds in these strains has never been described indicating that the clusters are expressed at a very low level or are silent under fermentation conditions. Foxicin A acts as a siderophore through interacting with ferric ions. Furthermore, it is a weak inhibitor of the aerobic respiratory chain and shows moderate antibiotic activity. The wide distribution of the cluster and the various properties of the compound indicate a major role of foxicins in strains.