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4-Hydroxybenzoic acid is a diffusible factor that connects metabolic shikimate pathway to the biosynthesis of a unique antifungal metabolite in Lysobacter enzymogenes

文献类型： 外文期刊

作者： Su, Zhenhe 1 ; Chen, Hongfu 1 ; Wang, Ping 1 ; Tombosa, Simon 3 ; Du, Liangcheng 3 ; Han, Yong 3 ; Shen, Yuemao; Qian, 1 ;

作者机构： 1.Nanjing Agr Univ, Minist Educ, Coll Plant Protect, Dept Plant Pathol,Key Lab Integrated Management C, Nanjing 210095, Jiangsu, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Plant Protect, Dept Plant Pathol, Nanjing 210014, Jiangsu, Peoples R China

3.Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA

4.Shandong Univ, Sch Pharmaceut Sci, Dept Nat Prod, Key

期刊名称：MOLECULAR MICROBIOLOGY （ 影响因子：3.501； 五年影响因子：3.996 ）

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收录情况： SCI

摘要： Heat-stable antifungal factor ( HSAF) produced by Lysobacter enzymogenes is a potential lead compound for developing new antibiotics. Yet, how L. enzymogenes regulates the HSAF biosynthesis remains largely unknown. Here, we show that 4hydroxybenzoic acid (4-HBA) serves as a diffusible factor for regulating HSAF biosynthesis. The biosynthesis of 4-HBA involved an oxygenase, LenB2, and mutation of lenB2 almost completely abolished 4HBA production, leading to significantly impaired HSAF production. Introduction of a heterologous gene coding for 4-HBA biosynthetic enzyme into the lenB2 mutant restored the production of 4-HBA and HSAF to their corresponding wild-type levels. Exogenous addition of 0.5-1lM 4-HBA was sufficient to restore HSAF production in the lenB2 mutant. Furthermore, the shikimate pathway was found to regulate the biosynthesis of HSAF via 4-HBA. Finally, we identified a LysR-family transcription factor (LysRLe) with activity directed to HSAF production. LysRLe could bind to the HSAF promoter and, as a result, regulates expression of HSAF biosynthesis genes. The 4-HBA could bind to LysRLe and appeared to partly enhance formation of the LysRLe-DNA complex. Collectively, our findings suggest that L. enzymogenes produces 4-HBA to serve as an adaptor molecule to link the shikimate pathway to the biosynthesis of a unique antifungal metabolite (HSAF).

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