Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes.
Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes.
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DOI：
10.1007/s00253-014-6120-x
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发表时间：
2015-01
影响因子：
5
通讯作者：
Du, Liangcheng
中科院分区：
文献类型：
--
作者：
Han, Yong;Wang, Yan;Tombosa, Simon;Wright, Stephen;Huffman, Justin;Yuen, Gary;Qian, Guoliang;Liu, Fengquan;Shen, Yuemao;Du, Liangcheng
溶杆菌属正在成为抗生素的新来源。这些抗生素的监管尚不清楚。在这里，我们鉴定了一种小分子代谢物（LeDSF3），它调节抗真菌抗生素HSAF（热稳定抗真菌因子）的生物合成，HSAF是一种多环四酸酯大环内酰胺，其结构和作用方式与现有抗真菌药物不同。 LeDSF3是从L. enzymogenes的培养液中分离出来的，并通过NMR和MS确定了其化学结构。纯化的化合物在野油菜黄单胞菌报告菌株中诱导绿色荧光，该菌株含有受 DSF（扩散信号因子）诱导型启动子控制的 gfp 基因。在 L. enzymogenes 培养物中外源添加 LeDSF3 显着增加了 HSAF 产量、HSAF 生物合成基因的转录以及生物体的抗真菌活性。 LeDSF3 调节的 HSAF 产生依赖于双组分调节系统 RpfC/RpfG。此外，LeDSF3 上调全局调节因子 Clp（cAMP 受体样蛋白）的表达。 clp 的中断导致 HSAF 停止生产。总之，结果表明 LeDSF3 是一种脂肪酸衍生的可扩散信号因子，正向调节 HSAF 生物合成，并且该信号传导由 RfpC/RpfG-Clp 途径介导。这些发现可能有助于通过应用遗传学和分子生物技术在溶杆菌（一组普遍存在但尚未充分开发的微生物）中生产抗生素。
Lysobacter species are emerging as new sources of antibiotics. The regulation of these antibiotics is not well understood. Here, we identified a small molecule metabolite (LeDSF3) that regulates the biosynthesis of the antifungal antibiotic HSAF (heat-stable antifungal factor), a polycyclic tetramate macrolactam with a structure and mode of action distinct from the existing antifungal drugs. LeDSF3 was isolated from the culture broth of L. enzymogenes, and its chemical structure was established by NMR and MS. The purified compound induced green fluorescence in a reporter strain of Xanthomonas campestris, which contained gfp gene under the control of a DSF (diffusible signaling factor)-inducible promoter. Exogenous addition of LeDSF3 in L. enzymogenes cultures significantly increased the HSAF yield, the transcription of HSAF biosynthetic genes, and the antifungal activity of the organism. The LeDSF3-regulated HSAF production is dependent on the two-component regulatory system RpfC/RpfG. Moreover, LeDSF3 up-regulated the expression of the global regulator Clp (cAMP receptor-like protein). The disruption of clp led to no HSAF production. Together, the results show that LeDSF3 is a fatty acid-derived, diffusible signaling factor positively regulating HSAF biosynthesis and that the signaling is mediated by the RfpC/RpfG-Clp pathway. These findings may facilitate the antibiotic production through applied genetics and molecular biotechnology in Lysobacter, a group of ubiquitous yet underexplored microorganisms.
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影响因子：
11
作者：
Boon, Calvin;Deng, Yinyue;Zhang, Lian-Hui
通讯作者：
Zhang, Lian-Hui
DOI：
10.1073/pnas.0805530105
发表时间：
2008-11-11
影响因子：
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通讯作者：
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影响因子：
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通讯作者：
Du, Liangcheng
影响因子：
2.6
作者：
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通讯作者：
Zinjarde, Smita S.