title: Wide Distribution of Foxicin Biosynthetic Gene Clusters inStreptomycesStrains - An Unusual Secondary Metabolite with Various Properties.
abstract: Streptomyces diastatochromogenesTü6028 is known to produce the polyketide antibiotic polyketomycin. The deletion of thepokOIVoxygenase 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 ofS. diastatochromogenes. The cluster spans 57 kb and encodes three PKS type I modules, one NRPS module and 41 additional enzymes. AfoxBIIgene-inactivated mutant ofS. diastatochromogenesTü6028 ΔpokOIVis unable to produce foxicins. Homologousfoxbiosynthetic gene clusters were found in more than 20 additionalStreptomycesstrains, overall in about 2.6% of all sequencedStreptomycesgenomes. 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 theEscherichia coliaerobic 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 inStreptomycesstrains.
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Greule
authors.affiliation: Department of Pharmaceutical and Medical Chemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Marolt
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Deubel
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Peintner
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Songya
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Jessen-Trefzer
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of FreiburgFreiburg im Breisgau, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of FreiburgFreiburg im Breisgau, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: De Ford
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Burschel
authors.affiliation: Department of Pharmaceutical Biology, Philipps-University Marburg Marburg, Germany.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Li
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
authors.affiliation: Department of Pharmaceutical and Medical Chemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Lüdeke
authors.affiliation: Department of Pharmaceutical and Medical Chemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bisel
authors.affiliation: Department of Pharmaceutical and Medical Chemistry, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Chemistry and Biology, University of Siegen Siegen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Paululat
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University of Freiburg Freiburg im Breisgau, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bechthold
keywords: Streptomyces; biosynthetic gene cluster; evolution; foxicin; natural product; siderophore