The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases

Wen Liu, Koichi Nonaka, Liping Nie, Jian Zhang, Steven D. Christenson, Juyun Bae, Steven G. Van Lanen, Emmanuel Zazopoulos, Chris M. Farnet, Catherine F. Yang, Ben Shen

Research output: Contribution to journalArticle

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Abstract

The biosynthetic gene cluster for the enediyne antitumor antibiotic neocarzinostatin (NCS) was localized to 130 kb continuous DNA from Streptomyces carzinostaticus ATCC15944 and confirmed by gene inactivation. DNA sequence analysis of 92 kb of the cloned region revealed 68 open reading frames (ORFs), 47 of which were determined to constitute the NCS cluster. Sequence analysis of the genes within the NCS cluster suggested dNDP-D-mannose as a precursor for the deoxy aminosugar, revealed two distinct type I polyketide synthases (PKSs), and supported a convergent model for NCS chromophore biosynthesis from the deoxy aminosugar, naphthoic acid, and enediyne core building blocks. These findings shed light into deoxysugar biosynthesis, further support the iterative type I PKS paradigm for enediyne core biosynthesis, and unveil a mechanism for microbial polycyclic aromatic polyketide biosynthesis by an iterative type I PKS.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalChemistry and Biology
Volume12
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Enediynes
Zinostatin
Polyketide Synthases
Biosynthesis
Streptomyces
Multigene Family
Genes
Polyketides
Gene Silencing
Mannose
DNA Sequence Analysis
Open Reading Frames
Sequence Analysis
DNA sequences
Anti-Bacterial Agents
DNA

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. / Liu, Wen; Nonaka, Koichi; Nie, Liping; Zhang, Jian; Christenson, Steven D.; Bae, Juyun; Van Lanen, Steven G.; Zazopoulos, Emmanuel; Farnet, Chris M.; Yang, Catherine F.; Shen, Ben.

In: Chemistry and Biology, Vol. 12, No. 3, 03.2005, p. 293-302.

Research output: Contribution to journalArticle

Liu, W, Nonaka, K, Nie, L, Zhang, J, Christenson, SD, Bae, J, Van Lanen, SG, Zazopoulos, E, Farnet, CM, Yang, CF & Shen, B 2005, 'The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases', Chemistry and Biology, vol. 12, no. 3, pp. 293-302. https://doi.org/10.1016/j.chembiol.2004.12.013
Liu, Wen ; Nonaka, Koichi ; Nie, Liping ; Zhang, Jian ; Christenson, Steven D. ; Bae, Juyun ; Van Lanen, Steven G. ; Zazopoulos, Emmanuel ; Farnet, Chris M. ; Yang, Catherine F. ; Shen, Ben. / The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. In: Chemistry and Biology. 2005 ; Vol. 12, No. 3. pp. 293-302.
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abstract = "The biosynthetic gene cluster for the enediyne antitumor antibiotic neocarzinostatin (NCS) was localized to 130 kb continuous DNA from Streptomyces carzinostaticus ATCC15944 and confirmed by gene inactivation. DNA sequence analysis of 92 kb of the cloned region revealed 68 open reading frames (ORFs), 47 of which were determined to constitute the NCS cluster. Sequence analysis of the genes within the NCS cluster suggested dNDP-D-mannose as a precursor for the deoxy aminosugar, revealed two distinct type I polyketide synthases (PKSs), and supported a convergent model for NCS chromophore biosynthesis from the deoxy aminosugar, naphthoic acid, and enediyne core building blocks. These findings shed light into deoxysugar biosynthesis, further support the iterative type I PKS paradigm for enediyne core biosynthesis, and unveil a mechanism for microbial polycyclic aromatic polyketide biosynthesis by an iterative type I PKS.",
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