The hedamycin locus implicates a novel aromatic PKS priming mechanism |
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Authors: | Bililign Tsion Hyun Chang-Gu Williams Jessica S Czisny Anne M Thorson Jon S |
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Institution: | Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA. |
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Abstract: | 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. |
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