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Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification

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Abstract

A biosynthetic gene cluster for chevalone E (1) and its oxidized derivatives have been identified within the genome of the endophytic fungus Aspergillus versicolor 0312, by a mining strategy targeting a polyketide-diterpenoid hybrid molecule. The biosynthetic pathway has been successfully reconstituted in the heterologous fungus Aspergillus oryzae. Interestingly, two P450 monooxygenases, Cle2 and Cle4, were found to transform 1 into seven new analogues including 7 and 8 that possess a unique five-membered lactone ring. Furthermore, the replacement of the terpene cyclase gene with that from another fungus led to the production of sartorypyrone D (11), which has a monocyclic terpenoid moiety. Finally, some of the compounds obtained in this study synergistically enhanced the cytotoxicity of doxorubicin (DOX) in breast cancer cells.

Graphical abstract: Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification

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Publication details

The article was received on 17 Oct 2018, accepted on 29 Nov 2018 and first published on 29 Nov 2018


Article type: Research Article
DOI: 10.1039/C8QO01124A
Citation: Org. Chem. Front., 2019, Advance Article
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    Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification

    W. Wang, L. Du, S. Sheng, A. Li, Y. Li, G. Cheng, G. Li, G. Sun, Q. Hu and Y. Matsuda, Org. Chem. Front., 2019, Advance Article , DOI: 10.1039/C8QO01124A

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