The hedamycin locus implicates a novel aromatic PKS priming mechanism.
The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber. Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketide synthase (PKS) genes, and two putative C-glycosyltransferase genes. As the first report of the cloning of the biosynthetic gene cluster for the pluramycin antibiotics, this work suggests that the biosynthesis of pluramycins utilize an iterative type I PKS system for the generation of a novel starter unit that subsequently primes the type II PKS system. It also implicates the involvement of a second catalytic ketosynthase (KSIII) to regulate this unusual priming step. Gene disruption is used to confirm the importance of both type I and II PKS genes for the biosynthesis of hedamycin.
Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.
Tsion
T
Bililign
Chang-Gu
CG
Hyun
Jessica S
JS
Williams
Anne M
AM
Czisny
Jon S
JS
Thorson
D000880:Anthraquinones / Q000378:metabolism*; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers; D008969:Molecular Sequence Data; D005810:Multigene Family; D048630:Polyketide Synthases / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics*
D000880:Anthraquinones; D017931:DNA Primers; C001328:hedamycin; D048630:Polyketide Synthases