Monooxygenase LaPhzX is Involved in Self-Resistance Mechanisms during the Biosynthesis of N-Oxide Phenazine Myxin
文献类型： 外文期刊
作者： Liu, Jiayu 1 ; Zhao, Yangyang 2 ; Fu, Zheng Qing 4 ; Liu, Fengquan 1 ;
作者机构： 1.Nanjing Agr Univ, Coll Plant Protect, Key Lab Integrated Management Crop Dis & Pests, Nanjing 210095, Peoples R China
2.Jiangsu Acad Agr Sci, Inst Plant Protect, Jiangsu Key Lab Food Qual, Nanjing 210014, Peoples R China
3.Minist Sci & Technol, Safety State Key Lab Cultivat Base, Nanjing 210014, Peoples R China
4.Univ South Carolina, Dept Biol Sci, Columbia, SC 29208 USA
关键词： phenazine; self-resistance; detoxification enzyme; Lysobacter antibioticus
期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.895； 五年影响因子：6.048 ）
ISSN： 0021-8561
年卷期： 2021 年 69 卷 45 期
页码：
收录情况： SCI
摘要： Self-resistance genes are deployed by many microbial producers of bioactive natural products to avoid self-toxicity. Myxin, a di-N-oxide phenazine produced by Lysobacter antibioticus OH13, is toxic to many microorganisms and tumor cells. Here, we uncovered a self-defense strategy featuring the antibiotic biosynthesis monooxygenase (ABM) family protein LaPhzX for myxin degradation. The gene LaPhzX is located in the myxin biosynthetic gene cluster (LaPhz), and its deletion resulted in bacterial mutants that are more sensitive to myxin. In addition, the LaPhzX mutants showed increased myxin accumulation and reduction of its derivative, compound 4, compared to the wild-type strain. Meanwhile, in vitro biochemical assays demonstrated that LaPhzX significantly degraded myxin in the presence of nicotinamide adenine dinucleotide phosphate (NADPH), nicotinamide adenine dinucleotide (NADH), flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). In addition, heterologous expression of LaPhzX in Xanthomonas oryzae pv. oryzae and Escherichia coli increased their resistance to myxin. Overall, our work illustrates a monooxygenase-mediated self-resistance mechanism for phenazine antibiotic biosynthesis.
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