Organisation of the biosynthetic gene cluster and tailoring enzymes in the biosynthesis of the tetracyclic quinone glycoside antibiotic polyketomycin.
Polyketomycin is a tetracyclic quinone glycoside produced by Streptomyces diastatochromogenes Tü6028. It shows cytotoxic and antibiotic activity, in particular against Gram-positive multi-drug-resistant strains (for example, MRSA). The polyketomycin biosynthetic gene cluster has been sequenced and characterised. Its identity was proven by inactivation of a alpha-ketoacyl synthase gene (pokP1) of the "minimal polyketide synthase II" system. In order to obtain valuable information about tailoring steps, we performed further gene-inactivation experiments. The generation of mutants with deletions in oxygenase genes (pokO1, pokO2, both in parallel and pokO4) and methyltransferase genes (pokMT1, pokMT2 and pokMT3) resulted in new polyketomycin derivatives, and provided information about the organisation of the biosynthetic pathway.
Daum
Martina
M
Albert-Ludwigs-Universität, Institut für Pharmazeutische Wissenschaften, Pharmazeutische Biologie und Biotechnologie, Freiburg, Germany.
Peintner
Iris
I
Linnenbrink
Anton
A
Frerich
Anke
A
Weber
Monika
M
Paululat
Thomas
T
Bechthold
Andreas
A
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D003001:Cloning, Molecular; D017353:Gene Deletion; D020868:Gene Silencing; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D015698:Genomic Library; D006027:Glycosides / Q000096:biosynthesis* / Q000737:chemistry; D006038:Glyoxylates / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics; D005810:Multigene Family; D010105:Oxygenases / Q000235:genetics; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D006027:Glycosides; D006038:Glyoxylates; C111268:polyketomycin; D048630:Polyketide Synthases; D010105:Oxygenases; D008780:Methyltransferases