Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System

X.M. Mao, Z.J. Zhan, M.N. Grayson, M.C. Tang, W. Xu, Y.Q. Li, W.B. Yin, H.C. Lin, Heng Chooi, K.N. Houk, Y. Tang

Research output: Contribution to journalArticle

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Abstract

© 2015 American Chemical Society. Aurovertins are fungal polyketides that exhibit potent inhibition of adenosine triphosphate synthase. Aurovertins contain a 2,6-dioxabicyclo[3.2.1]octane ring that is proposed to be derived from a polyene precursor through regioselective oxidations and epoxide openings. In this study, we identified only four enzymes required to produce aurovertin E. The core polyketide synthase produces a polyene α-pyrone. Following pyrone O-methylation by a methyltransferase, a flavin-dependent mono-oxygenase and an epoxide hydrolase can iteratively transform the terminal triene portion of the precursor into the dioxabicyclo[3.2.1]octane scaffold. We demonstrate that a tetrahydrofuranyl polyene is the first stable intermediate in the transformation, which can undergo epoxidation and anti-Baldwin 6-endo-tet ring opening to yield the cyclic ether product. Our results further demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex natural product scaffolds.
Original languageEnglish
Pages (from-to)11904-11907
JournalJournal of the American Chemical Society
Volume137
Issue number37
DOIs
Publication statusPublished - 2015

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Polyketides
Polyenes
Aurovertins
Biosynthesis
Pyrones
Scaffolds
Cyclic Ethers
Polyketide Synthases
Epoxide Hydrolases
Hydrolases
Oxygenases
Methylation
Epoxidation
Epoxy Compounds
Biosynthetic Pathways
Methyltransferases
Biological Products
Ethers
Enzymes
Adenosine Triphosphate

Cite this

Mao, X. M., Zhan, Z. J., Grayson, M. N., Tang, M. C., Xu, W., Li, Y. Q., ... Tang, Y. (2015). Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System. Journal of the American Chemical Society, 137(37), 11904-11907. https://doi.org/10.1021/jacs.5b07816
Mao, X.M. ; Zhan, Z.J. ; Grayson, M.N. ; Tang, M.C. ; Xu, W. ; Li, Y.Q. ; Yin, W.B. ; Lin, H.C. ; Chooi, Heng ; Houk, K.N. ; Tang, Y. / Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 37. pp. 11904-11907.
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Mao, XM, Zhan, ZJ, Grayson, MN, Tang, MC, Xu, W, Li, YQ, Yin, WB, Lin, HC, Chooi, H, Houk, KN & Tang, Y 2015, 'Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System' Journal of the American Chemical Society, vol. 137, no. 37, pp. 11904-11907. https://doi.org/10.1021/jacs.5b07816

Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System. / Mao, X.M.; Zhan, Z.J.; Grayson, M.N.; Tang, M.C.; Xu, W.; Li, Y.Q.; Yin, W.B.; Lin, H.C.; Chooi, Heng; Houk, K.N.; Tang, Y.

In: Journal of the American Chemical Society, Vol. 137, No. 37, 2015, p. 11904-11907.

Research output: Contribution to journalArticle

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T1 - Efficient Biosynthesis of Fungal Polyketides Containing the Dioxabicyclo-octane Ring System

AU - Mao, X.M.

AU - Zhan, Z.J.

AU - Grayson, M.N.

AU - Tang, M.C.

AU - Xu, W.

AU - Li, Y.Q.

AU - Yin, W.B.

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AU - Houk, K.N.

AU - Tang, Y.

PY - 2015

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AB - © 2015 American Chemical Society. Aurovertins are fungal polyketides that exhibit potent inhibition of adenosine triphosphate synthase. Aurovertins contain a 2,6-dioxabicyclo[3.2.1]octane ring that is proposed to be derived from a polyene precursor through regioselective oxidations and epoxide openings. In this study, we identified only four enzymes required to produce aurovertin E. The core polyketide synthase produces a polyene α-pyrone. Following pyrone O-methylation by a methyltransferase, a flavin-dependent mono-oxygenase and an epoxide hydrolase can iteratively transform the terminal triene portion of the precursor into the dioxabicyclo[3.2.1]octane scaffold. We demonstrate that a tetrahydrofuranyl polyene is the first stable intermediate in the transformation, which can undergo epoxidation and anti-Baldwin 6-endo-tet ring opening to yield the cyclic ether product. Our results further demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex natural product scaffolds.

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