The hedamycin locus implicates a novel aromatic PKS priming mechanism

Tsion Bililign; Chang Gu Hyun; Jessica S. Williams; Anne M. Czisny; Jon S. Thorson

doi:10.1016/j.chembiol.2004.04.016

The hedamycin locus implicates a novel aromatic PKS priming mechanism

Tsion Bililign, Chang Gu Hyun, Jessica S. Williams, Anne M. Czisny, Jon S. Thorson

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

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.

Original language	English
Pages (from-to)	959-969
Number of pages	11
Journal	Chemistry and Biology
Volume	11
Issue number	7
DOIs	https://doi.org/10.1016/j.chembiol.2004.04.016
State	Published - Jul 2004

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Institutes of Health (CA84374 and GM58196).

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

Access to Document

10.1016/j.chembiol.2004.04.016

Cite this

@article{f19c3df4f26d4ec8bc5f1b10df0b47fc,

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.",

author = "Tsion Bililign and Hyun, {Chang Gu} and Williams, {Jessica S.} and Czisny, {Anne M.} and Thorson, {Jon S.}",

note = "Funding Information: This work was supported in part by grants from the National Institutes of Health (CA84374 and GM58196). ",

year = "2004",

month = jul,

doi = "10.1016/j.chembiol.2004.04.016",

language = "English",

volume = "11",

pages = "959--969",

number = "7",

}

TY - JOUR

T1 - The hedamycin locus implicates a novel aromatic PKS priming mechanism

AU - Bililign, Tsion

AU - Hyun, Chang Gu

AU - Williams, Jessica S.

AU - Czisny, Anne M.

AU - Thorson, Jon S.

N1 - Funding Information: This work was supported in part by grants from the National Institutes of Health (CA84374 and GM58196).

PY - 2004/7

Y1 - 2004/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=3343016696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3343016696&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2004.04.016

DO - 10.1016/j.chembiol.2004.04.016

M3 - Article

C2 - 15271354

AN - SCOPUS:3343016696

SN - 1074-5521

VL - 11

SP - 959

EP - 969

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 7

ER -

The hedamycin locus implicates a novel aromatic PKS priming mechanism

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this