Isolation of the lysolipin gene cluster of Streptomyces tendae Tü 4042.
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.
Lopez
Patricio
P
Mikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
Hornung
Andreas
A
Welzel
Katrin
K
Unsin
Claudia
C
Wohlleben
Wolfgang
W
Weber
Tilmann
T
Pelzer
Stefan
S
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
D014966:Xanthenes; C014075:lysolipin I