Multidisciplinary approaches shed light on biosynthesis and unusual structural features of the antimicrobial hybrid NRPS/PKS-synthesized albicidin

Albicidin is a potent DNA gyrase inhibitor produced by the sugarcane pathogenic bacterium Xanthomonas albilineans. It blocks the d ifferentiation of chloroplasts, resulting in appearance of narrow white stripes on sugarcane leaves that are characteristic of leaf scald d isease. Albicidin targets the bacterial gyrase by a mechanism that is different from the one of any other known DNA gyrases inhibitors [l]. It exhibits antibacterial activity at nanomolar concentrations against Escherichia coli and to a lower extent aga inst numerous human pathogenic bacteria [2]. A decade of intense work was necessary to decipher a lbicid in's biosynthetic pathway and to elucidate its astonishing never-seen-before structure. Albicidin is produced by a hybrid PKS/NRPS system. Such ribosome-independent systems cons ist of modular megasynthetases which operate in an assembly-line fashion to activate, modify and link mostly unusual aminoacid build ing blocks, fina lly resulting in complex bioactive peptide-like molecules. The structure of albicidin, which was predicted by fo rmer in silico sequence a nalyses of its PKS/ NRPS gene cluster [3], was ascertained by means of mass spectrometry and NMR spectroscopy. We demonstrated that a lbicidin exhibits a linear polyaromatic penta-peptidic structure containing the rare aminoacids para-aminobenzoate a nd cyanoalanine [4]. Insights into biosynthesis and structure of natural a nalogues of al bicidin will also be presented [5]. The determination of the structure of albicidin allowed the development of a protocol for the chemical synthesis of this complex molecule [6]. Consequently, new research, such as structureactivity relationship studies, will now be possible.

Bibliographic Details

Main Authors:	Cociancich, Stéphane, Pesic, Alexander, Petras, Daniel, Duplan, Sandrine, Hempel, Benjamin, Hügelland, Manuela, Kemper, Sebastien, Kerwat, Dennis, Kretz, Julian, Mainz, Andi, Marguerettaz, Mélanie, Noëll, Julie, Pieretti, Isabelle, Schubert, Vivien, Semsary, Siamak, Uhlmann, Stefanie, Vieweg, Laura, Von Eckardstein, Leonard, Rott, Philippe, Royer, Monique, Süssmuth, Roderich
Format:	conference_item biblioteca
Language:	eng
Published:	s.n.
Subjects:	Q60 - Traitement des produits agricoles non alimentaires, 000 - Autres thèmes, H20 - Maladies des plantes,
Online Access:	http://agritrop.cirad.fr/580815/ http://agritrop.cirad.fr/580815/1/Cociancich_AMP2016_v2.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!