Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

Yangyang Zhao; Guoliang Qian; Yonghao Ye; Stephen Wright; Haotong Chen; Yuemao Shen; Fengquan Liu; Liangcheng Du

doi:10.1021/acs.orglett.6b01089

Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

Yangyang Zhao, Guoliang Qian, Yonghao Ye, Stephen Wright, Haotong Chen, Yuemao Shen, Fengquan Liu, Liangcheng Du

Chemistry

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

73 Scopus citations

Abstract

Heterocyclic aromatic N-oxides often have potent biological activities, but the mechanism for aromatic N-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of LaPhzNO1 abolished all N-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer-Villiger flavoproteins but was shown to catazlye phenazine N-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine N5,N10-dioxide. LaPhzNO1 also catalyzed N-oxidation of 8-hydroxyquinoline.

Original language	English (US)
Pages (from-to)	2495-2498
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	10
DOIs	https://doi.org/10.1021/acs.orglett.6b01089
State	Published - May 20 2016

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.6b01089

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title = "Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus",

abstract = "Heterocyclic aromatic N-oxides often have potent biological activities, but the mechanism for aromatic N-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of LaPhzNO1 abolished all N-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer-Villiger flavoproteins but was shown to catazlye phenazine N-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine N5,N10-dioxide. LaPhzNO1 also catalyzed N-oxidation of 8-hydroxyquinoline.",

author = "Yangyang Zhao and Guoliang Qian and Yonghao Ye and Stephen Wright and Haotong Chen and Yuemao Shen and Fengquan Liu and Liangcheng Du",

note = "Funding Information: This work was supported in part by the NIH (R01AI097260), NSFC (31329005, 31371981, and 31572046), National Basic Research (973) program of China (2015CB150600), and Jiangsu Provincal Key Technology Support Program (BE2015354). Y.Z. was partially supported by China Scholarship Council. We thank Dr. Xiuli Wu for assistance in NMR data analysis, and Dr. Ronald Cerny and Kurt Wulser for assistance in LC-MS and GC-MS experiments Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

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doi = "10.1021/acs.orglett.6b01089",

language = "English (US)",

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T1 - Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

AU - Zhao, Yangyang

AU - Qian, Guoliang

AU - Ye, Yonghao

AU - Wright, Stephen

AU - Chen, Haotong

AU - Shen, Yuemao

AU - Liu, Fengquan

AU - Du, Liangcheng

N1 - Funding Information: This work was supported in part by the NIH (R01AI097260), NSFC (31329005, 31371981, and 31572046), National Basic Research (973) program of China (2015CB150600), and Jiangsu Provincal Key Technology Support Program (BE2015354). Y.Z. was partially supported by China Scholarship Council. We thank Dr. Xiuli Wu for assistance in NMR data analysis, and Dr. Ronald Cerny and Kurt Wulser for assistance in LC-MS and GC-MS experiments Publisher Copyright: © 2016 American Chemical Society.

PY - 2016/5/20

Y1 - 2016/5/20

N2 - Heterocyclic aromatic N-oxides often have potent biological activities, but the mechanism for aromatic N-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of LaPhzNO1 abolished all N-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer-Villiger flavoproteins but was shown to catazlye phenazine N-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine N5,N10-dioxide. LaPhzNO1 also catalyzed N-oxidation of 8-hydroxyquinoline.

AB - Heterocyclic aromatic N-oxides often have potent biological activities, but the mechanism for aromatic N-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of LaPhzNO1 abolished all N-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer-Villiger flavoproteins but was shown to catazlye phenazine N-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine N5,N10-dioxide. LaPhzNO1 also catalyzed N-oxidation of 8-hydroxyquinoline.

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Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

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