title: Isolation of the lysolipin gene cluster of Streptomyces tendae Tü 4042.
abstract: Streptomyces tendae Tü 4042 produces the aromatic polyketide antibiotic lysolipin. Lysolipin has strong antibacterial activity against a variety of multidrug-resistant pathogens. The complete lysolipin biosynthetic gene cluster was isolated and fully sequenced. Within a 42-kb genomic region, 42 genes were identified that code for a type II polyketide synthase (llpF, E, and D), cyclases (llpCI-CIII), methyltransferases (llpMI-MVI), a halogenase (llpH), an amidotransferase (llpA), a ferredoxin (llpK), a transporter (llpN) and regulatory proteins (llpRI-RV). In addition, 15 genes encoding enzymes involved in redox modifications of the polyketide precursor molecule (llpOI-OVIII, ZI-ZIV, U, L, and S) were present in the lysolipin biosynthetic gene cluster. With this high number of oxidoreductases, lysolipin is among the most highly modified aromatic polyketides known to date. The heterologous expression of the cluster in Streptomyces albus led to lysolipin production with a yield comparable to that of wild-type, indicating that all biosynthetic genes were successfully cloned.
authors.affiliation: Mikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Patricio
authors.initials: P
authors.lastname: Lopez
authors.forename: Andreas
authors.initials: A
authors.lastname: Hornung
authors.forename: Katrin
authors.initials: K
authors.lastname: Welzel
authors.forename: Claudia
authors.initials: C
authors.lastname: Unsin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Tilmann
authors.initials: T
authors.lastname: Weber
authors.forename: Stefan
authors.initials: S
authors.lastname: Pelzer
mesh_terms: D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010084:Oxidation-Reduction; D012015:Reference Standards; D013302:Streptomyces / Q000145:classification / Q000235:genetics*; D014966:Xanthenes / Q000737:chemistry / Q000378:metabolism
chemical_list: D014966:Xanthenes; C014075:lysolipin I