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Biosynthesis of fragin is controlled by a novel quorum sensing signal

Jenul, Christian and Sieber, Simon and Daeppen, Christophe and Lardi, Martina and Pessi, Gabriela and Hoepfner, Dominic and Neuburger, Markus and Linden, Anthony and Gademann, Karl and Eberl, Leo (2019) Biosynthesis of fragin is controlled by a novel quorum sensing signal. Nature communications. ISSN 2041-1723

Abstract

Members of the diazenium diolate class of natural compounds show great
potential for drug development. Yet, their biosynthesis has remained elusive to
date. Here we identify a gene cluster directing the biosynthesis of the diazenium
diolate compound fragin in the opportunistic pathogen Burkholderia
cenocepacia H111. Fragin is shown to be the major antifungal compound
produced by this bacterium. We also show that a subset of the fragin
biosynthetic genes is involved in the synthesis of a novel cell-to-cell signaling
molecule, valdiazen. RNA-Seq analysis revealed that valdiazen not only controls
its own and fragin biosynthesis but is a global regulator of more than 150 genes.
Homologs of the valdiazen biosynthesis genes are found in various bacteria
suggesting that valdiazen is the first member of a new class of signal molecules.
Using structural information, in silico prediction of enzymatic functions and
biochemical data we propose a biosynthesis route for fragin and valdiazen.

Item Type: Article
Date Deposited: 17 Apr 2018 00:45
Last Modified: 17 Apr 2018 00:45
URI: https://oak.novartis.com/id/eprint/32754

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