Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes

Verfasser / Beitragende:
[Yong Han, Yan Wang, Simon Tombosa, Stephen Wright, Justin Huffman, Gary Yuen, Guoliang Qian, Fengquan Liu, Yuemao Shen, Liangcheng Du]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/2(2015-01-01), 801-811
Format:
Artikel (online)
ID: 605505276
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024 7 0 |a 10.1007/s00253-014-6120-x  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-014-6120-x 
245 0 0 |a Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes  |h [Elektronische Daten]  |c [Yong Han, Yan Wang, Simon Tombosa, Stephen Wright, Justin Huffman, Gary Yuen, Guoliang Qian, Fengquan Liu, Yuemao Shen, Liangcheng Du] 
520 3 |a 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. 
540 |a Springer-Verlag Berlin Heidelberg, 2014 
690 7 |a Diffusible signaling factor  |2 nationallicence 
690 7 |a Natural product biosynthesis  |2 nationallicence 
690 7 |a Regulation  |2 nationallicence 
690 7 |a HSAF  |2 nationallicence 
690 7 |a Lysobacter enzymogenes  |2 nationallicence 
700 1 |a Han  |D Yong  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
700 1 |a Wang  |D Yan  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
700 1 |a Tombosa  |D Simon  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
700 1 |a Wright  |D Stephen  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
700 1 |a Huffman  |D Justin  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
700 1 |a Yuen  |D Gary  |u Department of Plant Pathology, University of Nebraska—Lincoln, 68583, Lincoln, NE, USA  |4 aut 
700 1 |a Qian  |D Guoliang  |u College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China  |4 aut 
700 1 |a Liu  |D Fengquan  |u College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China  |4 aut 
700 1 |a Shen  |D Yuemao  |u Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, 250100, Jinan, China  |4 aut 
700 1 |a Du  |D Liangcheng  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/2(2015-01-01), 801-811  |x 0175-7598  |q 99:2<801  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-014-6120-x  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-014-6120-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Han  |D Yong  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Yan  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tombosa  |D Simon  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wright  |D Stephen  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Huffman  |D Justin  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yuen  |D Gary  |u Department of Plant Pathology, University of Nebraska—Lincoln, 68583, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Qian  |D Guoliang  |u College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Fengquan  |u College of Plant Protection, Nanjing Agricultural University, 210095, Nanjing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Shen  |D Yuemao  |u Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, 250100, Jinan, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Du  |D Liangcheng  |u Department of Chemistry, University of Nebraska—Lincoln, 68588, Lincoln, NE, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/2(2015-01-01), 801-811  |x 0175-7598  |q 99:2<801  |1 2015  |2 99  |o 253