A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation.
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.
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Lingxin
L
Kong
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Weike
W
Zhang
School of Chemistry and Biochemistry, University of Western Australia, Perth, WA 6009, Australia.
Yit Heng
YH
Chooi
Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China.
Lu
L
Wang
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Bo
B
Cao
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Zixin
Z
Deng
Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China.
Yiwen
Y
Chu
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: dlyou@sjtu.edu.cn.
Delin
D
You
D055162:Biocatalysis; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015394:Molecular Structure; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology*; D044004:Xanthones / Q000737:chemistry / Q000378:metabolism*
D061065:Polyketides; D044004:Xanthones; C573547:xantholipin; C009689:xanthone; D006899:Mixed Function Oxygenases