4-Hydroxybenzoic acid is a diffusible factor that connects metabolic shikimate pathway to the biosynthesis of a unique antifungal metabolite in Lysobacter enzymogenes
4-Hydroxybenzoic acid is a diffusible factor that connects metabolic shikimate pathway to the biosynthesis of a unique antifungal metabolite in Lysobacter enzymogenes
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4-羟基苯甲酸是一种扩散因子，将代谢莽草酸途径与溶杆菌酶基因中独特的抗真菌代谢物的生物合成联系起来
DOI：
10.1111/mmi.13619
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发表时间：
2017-04-01
影响因子：
3.6
通讯作者：
Liu, Fengquan
中科院分区：
文献类型：
--
作者：
Su, Zhenhe;Chen, Hongfu;Liu, Fengquan
酶原溶杆菌产生的热稳定抗真菌因子（HSAF）是开发新型抗生素的潜在先导化合物。然而，酵素乳杆菌如何调节HSAF的生物合成仍是未知的。在这里，我们发现4-羟基苯甲酸（4-HBA）是调节HSAF生物合成的扩散因子。4-HBA的生物合成涉及一种加氧酶LenB2，而LenB2的突变几乎完全消除了4HBA的产生，导致HSAF的产生显著受损。将编码4-HBA生物合成酶的异源基因导入lenB2突变体后，4-HBA和HSAF的产量恢复到相应的野生型水平。外源添加0.5-1lM 4-HBA足以恢复lenB2突变体中HSAF的产生。此外，还发现莽草酸途径通过4-HBA调节HSAF的生物合成。最后，我们确定了一个lysr家族转录因子（LysRLe），其活性直接导向HSAF的产生。LysRLe可以结合HSAF启动子，从而调控HSAF生物合成基因的表达。4-HBA可以与LysRLe结合，并在一定程度上促进了LysRLe- dna复合物的形成。总的来说，我们的研究结果表明，L.酶原菌产生4-HBA作为一个适配器分子，将莽草酸途径与一种独特的抗真菌代谢物（HSAF）的生物合成联系起来。
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).