A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation

L. Kong, W. Zhang, Heng Chooi, L. Wang, B. Cao, Z. Deng, Y. Chu, D. You

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

© 2016 Elsevier Ltd. All rights reserved. Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular, fused hexacyclic system. In this study, we demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction. Moreover, characterizations of homologous FMOs of XanO4 suggested the generality of the XanO4-like-mediated reaction for the assembly of a xanthone ring in the biosynthesis of polycyclic xanthone antibiotics. These findings not only expand the repertoire of FMO activities but also reveal a novel mechanism for xanthone ring formation.
Original languageEnglish
Pages (from-to)508-516
Number of pages9
JournalCell Chemical Biology
Volume23
Issue number4
DOIs
Publication statusPublished - 2016

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Biosynthesis
Mixed Function Oxygenases
Anti-Bacterial Agents
Anthraquinones
Labeling
xanthone
xantholipin
Oxygen
Atoms
Experiments

Cite this

Kong, L. ; Zhang, W. ; Chooi, Heng ; Wang, L. ; Cao, B. ; Deng, Z. ; Chu, Y. ; You, D. / A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation. In: Cell Chemical Biology. 2016 ; Vol. 23, No. 4. pp. 508-516.
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A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation. / Kong, L.; Zhang, W.; Chooi, Heng; Wang, L.; Cao, B.; Deng, Z.; Chu, Y.; You, D.

In: Cell Chemical Biology, Vol. 23, No. 4, 2016, p. 508-516.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Kong, L.

AU - Zhang, W.

AU - Chooi, Heng

AU - Wang, L.

AU - Cao, B.

AU - Deng, Z.

AU - Chu, Y.

AU - You, D.

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N2 - © 2016 Elsevier Ltd. All rights reserved. Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular, fused hexacyclic system. In this study, we demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction. Moreover, characterizations of homologous FMOs of XanO4 suggested the generality of the XanO4-like-mediated reaction for the assembly of a xanthone ring in the biosynthesis of polycyclic xanthone antibiotics. These findings not only expand the repertoire of FMO activities but also reveal a novel mechanism for xanthone ring formation.

AB - © 2016 Elsevier Ltd. All rights reserved. Xantholipin and several related polycyclic xanthone antibiotics feature a unique xanthone ring nucleus within a highly oxygenated, angular, fused hexacyclic system. In this study, we demonstrated that a flavin-dependent monooxygenase (FMO) XanO4 catalyzes the oxidative transformation of an anthraquinone to a xanthone system during the biosynthesis of xantholipin. In vitro isotopic labeling experiments showed that the reaction involves sequential insertion of two oxygen atoms, accompanied by an unexpected cryptic demethoxylation reaction. Moreover, characterizations of homologous FMOs of XanO4 suggested the generality of the XanO4-like-mediated reaction for the assembly of a xanthone ring in the biosynthesis of polycyclic xanthone antibiotics. These findings not only expand the repertoire of FMO activities but also reveal a novel mechanism for xanthone ring formation.

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JF - Cell Chemical Biology

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