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

doi:10.1016/j.chembiol.2016.03.013

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

School of Molecular Sciences

Research output: Contribution to journal › Article

9 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 language	English
Pages (from-to)	508-516
Number of pages	9
Journal	Cell Chemical Biology
Volume	23
Issue number	4
DOIs	https://doi.org/10.1016/j.chembiol.2016.03.013
Publication status	Published - 2016

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Kong, L., Zhang, W., Chooi, H., Wang, L., Cao, B., Deng, Z., ... You, D. (2016). A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation. Cell Chemical Biology, 23(4), 508-516. https://doi.org/10.1016/j.chembiol.2016.03.013

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title = "A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation",

abstract = "{\circledC} 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.",

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

year = "2016",

doi = "10.1016/j.chembiol.2016.03.013",

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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.

PY - 2016

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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.

U2 - 10.1016/j.chembiol.2016.03.013

DO - 10.1016/j.chembiol.2016.03.013

M3 - Article

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VL - 23

SP - 508

EP - 516

JO - Cell Chemical Biology

JF - Cell Chemical Biology

SN - 2451-9456

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10.1016/j.chembiol.2016.03.013