Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement

Guixi Gao; Xiangyang Liu; Min Xu; Yemin Wang; Fei Zhang; Lijun Xu; Jin Lv; Qingshan Long; Qianjin Kang; Hong Yu Ou; Ying Wang; Jürgen Rohr; Zixin Deng; Ming Jiang; Shuangjun Lin; Meifeng Tao

doi:10.1016/j.chembiol.2017.06.008

Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement

Guixi Gao, Xiangyang Liu, Min Xu, Yemin Wang, Fei Zhang, Lijun Xu, Jin Lv, Qingshan Long, Qianjin Kang, Hong Yu Ou, Ying Wang, Jürgen Rohr, Zixin Deng, Ming Jiang, Shuangjun Lin, Meifeng Tao

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Bacterial aromatic polyketides are a group of natural products synthesized by polyketide synthases (PKSs) that show diverse structures and biological activities. They are structurally subclassified into linear, angular, and discoid aromatic polyketides, the formation of which is commonly determined by the shaping and folding of the poly-β-keto intermediates under the concerted actions of the minimal PKSs, cyclases and ketoreductases. Murayaquinone, found in several streptomycetes, possesses an unusual tricyclic angular aromatic polyketide core containing a 9,10-phenanthraquinone. In this study, genes essential for murayaquinone biosynthesis were identified, and a linear anthraoxirene intermediate was discovered. A unique biosynthetic model for the angular aromatic polyketide formation was discovered and confirmed through in vivo and in vitro studies. Three oxidoreductases, MrqO3, MrqO6, and MrqO7, were identified to catalyze the conversion of the linear aromatic polyketide intermediate into the final angularly arranged framework, which exemplifies a novel strategy for the biosynthesis of angular aromatic polyketides.

Original language	English
Pages (from-to)	881-891.e4
Journal	Cell Chemical Biology
Volume	24
Issue number	7
DOIs	https://doi.org/10.1016/j.chembiol.2017.06.008
State	Published - Jul 20 2017

Bibliographical note

Funding Information:
We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF (31370134, 31425001, 31300033, and 21661140002) of China, and the MOST (2012CB721000; 2010AA10A201; Chinese-Australia Joint Grant: 2016YFE0101000), the US NIH (grant R01 GM 105977), and the Science and Technology Commission of Shanghai Municipality (15JC1400401).

Funding Information:
We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF ( 31370134 , 31425001 , 31300033 , and 21661140002 ) of China, and the MOST ( 2012CB721000 ; 2010AA10A201 ; Chinese-Australia Joint Grant: 2016YFE0101000 ), the US NIH (grant R01 GM 105977 ), and the Science and Technology Commission of Shanghai Municipality ( 15JC1400401 ).

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

Baeyer-Villiger oxygenase
angular aromatic polyketides
anthracenone epoxide
biosynthetic pathway
murayaquinone
oxidative rearrangement
oxidoreductase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2017.06.008

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@article{273c685875f846c19eb105c97bb7f18e,

title = "Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement",

abstract = "Bacterial aromatic polyketides are a group of natural products synthesized by polyketide synthases (PKSs) that show diverse structures and biological activities. They are structurally subclassified into linear, angular, and discoid aromatic polyketides, the formation of which is commonly determined by the shaping and folding of the poly-β-keto intermediates under the concerted actions of the minimal PKSs, cyclases and ketoreductases. Murayaquinone, found in several streptomycetes, possesses an unusual tricyclic angular aromatic polyketide core containing a 9,10-phenanthraquinone. In this study, genes essential for murayaquinone biosynthesis were identified, and a linear anthraoxirene intermediate was discovered. A unique biosynthetic model for the angular aromatic polyketide formation was discovered and confirmed through in vivo and in vitro studies. Three oxidoreductases, MrqO3, MrqO6, and MrqO7, were identified to catalyze the conversion of the linear aromatic polyketide intermediate into the final angularly arranged framework, which exemplifies a novel strategy for the biosynthesis of angular aromatic polyketides.",

keywords = "Baeyer-Villiger oxygenase, angular aromatic polyketides, anthracenone epoxide, biosynthetic pathway, murayaquinone, oxidative rearrangement, oxidoreductase",

author = "Guixi Gao and Xiangyang Liu and Min Xu and Yemin Wang and Fei Zhang and Lijun Xu and Jin Lv and Qingshan Long and Qianjin Kang and Ou, {Hong Yu} and Ying Wang and J{\"u}rgen Rohr and Zixin Deng and Ming Jiang and Shuangjun Lin and Meifeng Tao",

note = "Funding Information: We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF (31370134, 31425001, 31300033, and 21661140002) of China, and the MOST (2012CB721000; 2010AA10A201; Chinese-Australia Joint Grant: 2016YFE0101000), the US NIH (grant R01 GM 105977), and the Science and Technology Commission of Shanghai Municipality (15JC1400401). Funding Information: We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF ( 31370134 , 31425001 , 31300033 , and 21661140002 ) of China, and the MOST ( 2012CB721000 ; 2010AA10A201 ; Chinese-Australia Joint Grant: 2016YFE0101000 ), the US NIH (grant R01 GM 105977 ), and the Science and Technology Commission of Shanghai Municipality ( 15JC1400401 ). Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

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doi = "10.1016/j.chembiol.2017.06.008",

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T1 - Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement

AU - Gao, Guixi

AU - Liu, Xiangyang

AU - Xu, Min

AU - Wang, Yemin

AU - Zhang, Fei

AU - Xu, Lijun

AU - Lv, Jin

AU - Long, Qingshan

AU - Kang, Qianjin

AU - Ou, Hong Yu

AU - Wang, Ying

AU - Rohr, Jürgen

AU - Deng, Zixin

AU - Jiang, Ming

AU - Lin, Shuangjun

AU - Tao, Meifeng

N1 - Funding Information: We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF (31370134, 31425001, 31300033, and 21661140002) of China, and the MOST (2012CB721000; 2010AA10A201; Chinese-Australia Joint Grant: 2016YFE0101000), the US NIH (grant R01 GM 105977), and the Science and Technology Commission of Shanghai Municipality (15JC1400401). Funding Information: We thank Songwang Hou, Tianshen Tao, and Colin P. Smith for gifts of bacterial strains. This work was supported by NSF ( 31370134 , 31425001 , 31300033 , and 21661140002 ) of China, and the MOST ( 2012CB721000 ; 2010AA10A201 ; Chinese-Australia Joint Grant: 2016YFE0101000 ), the US NIH (grant R01 GM 105977 ), and the Science and Technology Commission of Shanghai Municipality ( 15JC1400401 ). Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017/7/20

Y1 - 2017/7/20

N2 - Bacterial aromatic polyketides are a group of natural products synthesized by polyketide synthases (PKSs) that show diverse structures and biological activities. They are structurally subclassified into linear, angular, and discoid aromatic polyketides, the formation of which is commonly determined by the shaping and folding of the poly-β-keto intermediates under the concerted actions of the minimal PKSs, cyclases and ketoreductases. Murayaquinone, found in several streptomycetes, possesses an unusual tricyclic angular aromatic polyketide core containing a 9,10-phenanthraquinone. In this study, genes essential for murayaquinone biosynthesis were identified, and a linear anthraoxirene intermediate was discovered. A unique biosynthetic model for the angular aromatic polyketide formation was discovered and confirmed through in vivo and in vitro studies. Three oxidoreductases, MrqO3, MrqO6, and MrqO7, were identified to catalyze the conversion of the linear aromatic polyketide intermediate into the final angularly arranged framework, which exemplifies a novel strategy for the biosynthesis of angular aromatic polyketides.

AB - Bacterial aromatic polyketides are a group of natural products synthesized by polyketide synthases (PKSs) that show diverse structures and biological activities. They are structurally subclassified into linear, angular, and discoid aromatic polyketides, the formation of which is commonly determined by the shaping and folding of the poly-β-keto intermediates under the concerted actions of the minimal PKSs, cyclases and ketoreductases. Murayaquinone, found in several streptomycetes, possesses an unusual tricyclic angular aromatic polyketide core containing a 9,10-phenanthraquinone. In this study, genes essential for murayaquinone biosynthesis were identified, and a linear anthraoxirene intermediate was discovered. A unique biosynthetic model for the angular aromatic polyketide formation was discovered and confirmed through in vivo and in vitro studies. Three oxidoreductases, MrqO3, MrqO6, and MrqO7, were identified to catalyze the conversion of the linear aromatic polyketide intermediate into the final angularly arranged framework, which exemplifies a novel strategy for the biosynthesis of angular aromatic polyketides.

KW - Baeyer-Villiger oxygenase

KW - angular aromatic polyketides

KW - anthracenone epoxide

KW - biosynthetic pathway

KW - murayaquinone

KW - oxidative rearrangement

KW - oxidoreductase

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AN - SCOPUS:85023635182

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VL - 24

SP - 881-891.e4

JO - Cell Chemical Biology

JF - Cell Chemical Biology

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ER -

Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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