Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp.

Yousong Ding; Jeffrey R.De Wet; James Cavalcoli; Shengying Li; Thomas J. Greshock; Kenneth A. Miller; Jennifer M. Finefield; James D. Sunderhaus; Timothy J. McAfoos; Sachiko Tsukamoto; Robert M. Williams; David H. Sherman

doi:10.1021/ja1049302

Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp.

Yousong Ding, Jeffrey R.De Wet, James Cavalcoli, Shengying Li, Thomas J. Greshock, Kenneth A. Miller, Jennifer M. Finefield, James D. Sunderhaus, Timothy J. McAfoos, Sachiko Tsukamoto, Robert M. Williams, David H. Sherman

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

102 Scopus citations

Abstract

Stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing a core bicyclo[2.2.2]diazaoctane ring system. These bioactive fungal secondary metabolites have a range of unusual structural and stereochemical features but their biosynthesis has remained uncharacterized. Herein, we report the first biosynthetic gene cluster for this class of fungal alkaloids based on whole genome sequencing of a marine-derived Aspergillus sp. Two central pathway enzymes catalyzing both normal and reverse prenyltransfer reactions were characterized in detail. Our results establish the early steps for creation of the prenylated indole alkaloid structure and suggest a scheme for the biosynthesis of stephacidin and notoamide metabolites. The work provides the first genetic and biochemical insights for understanding the structural diversity of this important family of fungal alkaloids.

Original language	English (US)
Pages (from-to)	12733-12740
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	132
Issue number	36
DOIs	https://doi.org/10.1021/ja1049302
State	Published - Sep 15 2010
Externally published	Yes

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja1049302

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Ding, Y., Wet, J. R. D., Cavalcoli, J., Li, S., Greshock, T. J., Miller, K. A., Finefield, J. M., Sunderhaus, J. D., McAfoos, T. J., Tsukamoto, S., Williams, R. M., & Sherman, D. H. (2010). Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp. Journal of the American Chemical Society, 132(36), 12733-12740. https://doi.org/10.1021/ja1049302

Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp. / Ding, Yousong; Wet, Jeffrey R.De; Cavalcoli, James et al.
In: Journal of the American Chemical Society, Vol. 132, No. 36, 15.09.2010, p. 12733-12740.

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

Ding, Y, Wet, JRD, Cavalcoli, J, Li, S, Greshock, TJ, Miller, KA, Finefield, JM, Sunderhaus, JD, McAfoos, TJ, Tsukamoto, S, Williams, RM & Sherman, DH 2010, 'Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp.', Journal of the American Chemical Society, vol. 132, no. 36, pp. 12733-12740. https://doi.org/10.1021/ja1049302

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abstract = "Stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing a core bicyclo[2.2.2]diazaoctane ring system. These bioactive fungal secondary metabolites have a range of unusual structural and stereochemical features but their biosynthesis has remained uncharacterized. Herein, we report the first biosynthetic gene cluster for this class of fungal alkaloids based on whole genome sequencing of a marine-derived Aspergillus sp. Two central pathway enzymes catalyzing both normal and reverse prenyltransfer reactions were characterized in detail. Our results establish the early steps for creation of the prenylated indole alkaloid structure and suggest a scheme for the biosynthesis of stephacidin and notoamide metabolites. The work provides the first genetic and biochemical insights for understanding the structural diversity of this important family of fungal alkaloids.",

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AU - Li, Shengying

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AU - Miller, Kenneth A.

AU - Finefield, Jennifer M.

AU - Sunderhaus, James D.

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AU - Williams, Robert M.

AU - Sherman, David H.

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Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived aspergillus sp.

Abstract

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