Distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway crosstalk
書誌事項
- 公開日
- 2013-10-13
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/nchembio.1366
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
Spirotryprostatins, an indole alkaloid class of nonribosomal peptides isolated from Aspergillus fumigatus, are known for their antimitotic activity in tumor cells. Because spirotryprostatins and many other chemically complex spiro-carbon-bearing natural products exhibit useful biological activities, identifying and understanding the mechanism of spiro-carbon biosynthesis is of great interest. Here we report a detailed study of spiro-ring formation in spirotryprostatins from tryprostatins derived from the fumitremorgin biosynthetic pathway, using reactants and products prepared with engineered yeast and fungal strains. Unexpectedly, FqzB, an FAD-dependent monooxygenase from the unrelated fumiquinazoline biosynthetic pathway, catalyzed spiro-carbon formation in spirotryprostatin A via an epoxidation route. Furthermore, FtmG, a cytochrome P450 from the fumitremorgin biosynthetic pathway, was determined to catalyze the spiro-ring formation in spirotryprostatin B. Our results highlight the versatile role of oxygenating enzymes in the biosynthesis of structurally complex natural products and indicate that cross-talk of different biosynthetic pathways allows product diversification in natural product biosynthesis.
収録刊行物
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- Nature Chemical Biology
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Nature Chemical Biology 9 (12), 818-825, 2013-10-13
Springer Science and Business Media LLC
