Authors: | Bililign, T.; Hyun, C. G.; Williams, J. S.; Czisny, A. M.; Thorson, J. S. |
Article Title: | The hedamycin locus implicates a novel aromatic PKS priming mechanism |
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. |
Keywords: | genetics; molecular genetics; metabolism; molecular cloning; cloning, molecular; molecular sequence data; nucleotide sequence; base sequence; dna primers; primer dna; chromosome map; chromosome mapping; multigene family; streptomyces; anthraquinones; anthraquinone derivative; hedamycin; polyketide synthase; polyketide synthases; article; streptomyces griseoruber |
Journal Title: | Chemistry and Biology |
Volume: | 11 |
Issue: | 7 |
ISSN: | 1074-5521 |
Publisher: | Elsevier Inc. |
Date Published: | 2004-07-01 |
Start Page: | 959 |
End Page: | 969 |
Language: | English |
DOI: | 10.1016/j.chembiol.2004.04.016 |
PROVIDER: | scopus |
PUBMED: | 15271354 |
DOI/URL: | |
Notes: | Chem. Biol. -- Cited By (since 1996):49 -- Export Date: 16 June 2014 -- CODEN: CBOLE -- Molecular Sequence Numbers: GENBANK: AY196994; -- Source: Scopus |