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

Wei-Guang Wang; Lian-Qiong Du; Shan-Ling Sheng; Ao Li; Yan-Ping Li; Gui-Guang Cheng; Gan-Peng Li; Guiling Sun; Qiu-Fen Hu; Yudai Matsuda

doi:10.1039/C8QO01124A

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

Wei-Guang Wang, Lian-Qiong Du, Shan-Ling Sheng, Ao Li, Yan-Ping Li, Gui-Guang Cheng, Gan-Peng Li, Guiling Sun, Qiu-Fen Hu, Yudai Matsuda^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

52 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	571-578
Journal	Organic Chemistry Frontiers
Volume	6
Issue number	5
Online published	29 Nov 2018
DOIs	https://doi.org/10.1039/C8QO01124A
Publication status	Published - 7 Mar 2019

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SDG 3 Good Health and Well-being

Publisher's Copyright Statement

COPYRIGHT TERMS OF DEPOSITED POSTPRINT FILE: This journal is © the Partner Organisations 2019. This is the accepted version of a paper published in Organic Chemistry Frontiers. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Wang, W.-G., Du, L.-Q., Sheng, S.-L., Li, A., Li, Y.-P., Cheng, G.-G., Li, G.-P., Sun, G., Hu, Q.-F., & Matsuda, Y. (2019). Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification. Organic Chemistry Frontiers, 6(5), 571-578. https://doi.org/10.1039/C8QO01124A

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

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.",

author = "Wei-Guang Wang and Lian-Qiong Du and Shan-Ling Sheng and Ao Li and Yan-Ping Li and Gui-Guang Cheng and Gan-Peng Li and Guiling Sun and Qiu-Fen Hu and Yudai Matsuda",

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Genome mining for fungal polyketide-diterpenoid hybrids: discovery of key terpene cyclases and multifunctional P450s for structural diversification. / Wang, Wei-Guang; Du, Lian-Qiong; Sheng, Shan-Ling et al.
In: Organic Chemistry Frontiers, Vol. 6, No. 5, 07.03.2019, p. 571-578.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Genome mining for fungal polyketide-diterpenoid hybrids

T2 - discovery of key terpene cyclases and multifunctional P450s for structural diversification

AU - Wang, Wei-Guang

AU - Du, Lian-Qiong

AU - Sheng, Shan-Ling

AU - Li, Ao

AU - Li, Yan-Ping

AU - Cheng, Gui-Guang

AU - Li, Gan-Peng

AU - Sun, Guiling

AU - Hu, Qiu-Fen

AU - Matsuda, Yudai

PY - 2019/3/7

Y1 - 2019/3/7

N2 - 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.

AB - 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.

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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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