Biosynthesis of fragin is controlled by a novel quorum sensing signal

Christian Jenul, Simon Sieber, Christophe Daeppen, Anugraha Mathew, Martina Lardi, Gabriella Pessi, Dominic Hoepfner, Markus Neuburger, Anthony Linden, Karl Gademann () and Leo Eberl ()
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Christian Jenul: University of Zurich
Simon Sieber: University of Zurich
Christophe Daeppen: University of Zurich
Anugraha Mathew: University of Zurich
Martina Lardi: University of Zurich
Gabriella Pessi: University of Zurich
Dominic Hoepfner: Novartis Institutes for BioMedical Research
Markus Neuburger: University of Basel
Anthony Linden: University of Zurich
Karl Gademann: University of Zurich
Leo Eberl: University of Zurich

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Members of the diazeniumdiolate class of natural compounds show potential for drug development because of their antifungal, antibacterial, antiviral, and antitumor activities. Yet, their biosynthesis has remained elusive to date. Here, we identify a gene cluster directing the biosynthesis of the diazeniumdiolate compound fragin in Burkholderia cenocepacia H111. We provide evidence that fragin is a metallophore and that metal chelation is the molecular basis of its antifungal activity. A subset of the fragin biosynthetic genes is involved in the synthesis of a previously undescribed cell-to-cell signal molecule, valdiazen. RNA-Seq analyses reveal that valdiazen controls fragin biosynthesis and affects the expression of more than 100 genes. Homologs of the valdiazen biosynthesis genes are found in various bacteria, suggesting that valdiazen-like compounds may constitute a new class of signal molecules. We use structural information, in silico prediction of enzymatic functions and biochemical data to propose a biosynthesis route for fragin and valdiazen.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03690-2

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DOI: 10.1038/s41467-018-03690-2

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