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Issue 5, 2019
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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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Supplementary files

Article information


Submitted
17 Oct 2018
Accepted
29 Nov 2018
First published
29 Nov 2018

Org. Chem. Front., 2019,6, 571-578
Article type
Research Article

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, 6, 571
DOI: 10.1039/C8QO01124A

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