Class II Lanthipeptides
Class III Lanthipeptides



Coworkers: Stefan Graetz, Dennis Kerwat, Leonard von Eckardstein

Keywords: Albicidin, Antibiotic, NRPS, PKS, mass spectrometry, NMR, biosynthesis, total synthesis,

Cooperation: Royer Lab, CIRAD, Montpellier, France



Albicidin is a potent DNA gyrase inhibitor, produced by the sugarcane invading bacterium Xanthomonas albilineans. After decades of investigations we were able to solve the hitherto unknown structure of albicidin by a combination of mass spectrometric and NMR techniques, revealing a unique polyaromatic oligopeptide mainly composed of p-amino benzoicacids and an unusual cyano-alanine residue [1,2]. In vitro studies of the biochemical synthesis machinery of albicidin provided detailed insights into this unique pathway of a hybrid polyketide synthase/ non-ribosomal peptide synthetase [2]. What makes albicidin interesting in the context of the search for novel anti-infectives is its very promising antibacterial activity against a wide range of Gram-positive and Gram-negative bacteria [1,3]. From Xanthomonas albilineans only limited amounts of albicidin can be obtained. Therefore we developed a total synthesis of albicidin to provide sufficient material for bioactivity profiling and structure-activity studies [3]. The convergent synthesis strategy builds up albicidins structure from three main building blocks. Thereby, the difficult formation of the peptide bonds between the aromatic amino acids was mediated by use of triphosgene. The total synthesis confirmed the elucidated structure and stereochemistry. The synthetic protocol provides multigram amounts of albicidin for further profiling of its drug properties.