The hedamycin locus implicates a novel aromatic PKS priming mechanism Journal Article


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
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Jon S Thorson
    22 Thorson