caa a22 4500 605505276 CHVBK 20210128100621.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00253-014-6120-x doi (NATIONALLICENCE)springer-10.1007/s00253-014-6120-x Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes [Elektronische Daten] [Yong Han, Yan Wang, Simon Tombosa, Stephen Wright, Justin Huffman, Gary Yuen, Guoliang Qian, Fengquan Liu, Yuemao Shen, Liangcheng Du] 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 heat-stable antifungal factor (HSAF), 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 Lysobacter 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 a gfp gene under the control of a diffusible signaling factor (DSF)-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 upregulated the expression of the global regulator cAMP receptor-like protein (Clp). 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. Springer-Verlag Berlin Heidelberg, 2014 Diffusible signaling factor nationallicence Natural product biosynthesis nationallicence Regulation nationallicence HSAF nationallicence Lysobacter enzymogenes nationallicence Han Yong Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Wang Yan Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Tombosa Simon Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Wright Stephen Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Huffman Justin Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Yuen Gary Department of Plant Pathology, University of Nebraska—Lincoln, 68583, Lincoln, NE, USA aut Qian Guoliang College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China aut Liu Fengquan College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China aut Shen Yuemao Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, 250100, Jinan, China aut Du Liangcheng Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/2(2015-01-01), 801-811 0175-7598 99:2<801 2015 99 253 https://doi.org/10.1007/s00253-014-6120-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-014-6120-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Han Yong Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Wang Yan Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Tombosa Simon Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Wright Stephen Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Huffman Justin Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Yuen Gary Department of Plant Pathology, University of Nebraska—Lincoln, 68583, Lincoln, NE, USA aut NATIONALLICENCE 700 1- Qian Guoliang College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China aut NATIONALLICENCE 700 1- Liu Fengquan College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China aut NATIONALLICENCE 700 1- Shen Yuemao Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, 250100, Jinan, China aut NATIONALLICENCE 700 1- Du Liangcheng Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/2(2015-01-01), 801-811 0175-7598 99:2<801 2015 99 253