Structural characterization of vanchrobactin, a new catechol siderophore produced by the fish pathogen Vibrio anguillarum serotype O2 Raquel G. Soengas, a Cristina Anta, b Alfonso Espada, b Vanessa Paz, a Isabel R. Ares, c Miguel Balado, c Jaime Rodrı ´guez, a Manuel L. Lemos c and Carlos Jime ´nez a, * a Departamento de Quı ´mica Fundamental, Facultad de Ciencias, Universidad de A Corun ˜a, A Corun ˜a E-15071, Spain b Analytical Technologies DCR&T Alcobendas, Lilly S.A., Avda. de la Industria 30, E-28108 Alcobendas/Madrid, Spain c Departamento de Microbiologia y Parasitologia, Instituto de Acuicultura, Universidad de Santiago de Compostela, Santiago de Compostela E-15782, Spain Received 20 June 2006; revised 6 July 2006; accepted 10 July 2006 Abstract—Vanchrobactin, a new catecol-type siderophore produced by cells of the fish pathogen Vibrio anguillarum serotype O2, has been isolated from the supernatants of iron-deficient cultures. Its structure was characterized from spectral data and established as N-[N 0 -(2,3-dihydroxybenzoyl)-arginyl]-serine. Ó 2006 Elsevier Ltd. All rights reserved. Iron acquisition is an indispensable process for most living organisms because it is required as a cofactor for enzymes involved in general metabolism, DNA replica- tion, as well as in the electron transport chain. 1 In spite of its abundance (5% of the earth crust), the availability of iron is dramatically limited by the very high insolubil- ity of Fe +3 at physiological pH. Since there is virtually no free iron available for bacterial growth, 2 bacterial patho- gens have evolved a number of mechanisms to overcome this iron restriction. The most common ‘biomachinery’ involves the synthesis and secretion of low molecular weight (300–2000 Da) high-affinity chelators to sequester Fe +3 , termed siderophores. 3 These molecules, generally excreted into the culture medium, are able to strongly chelate in a specific manner to solubilize and deliver Fe +3 into the cells. This process occurs via specific cell surface receptors using an ATP-dependent high-affinity transport system. 4 The bacterial fish pathogen Vibrio anguillarum is the causative agent of vibriosis, an extremely fatal hemor- rhagic septicaemia. This disease affects marine and freshwater fish species throughout the world that results in considerable economic losses in aquaculture farming worldwide. 5 Although there are more than 20 recog- nized serotypes, 6 those named O1 and O2 are the main ones implicated in the infections. 7 It is known that the ability to scavenge iron through the utilization of sidero- phores is a key factor in the virulence of this fish pathogen. 8 At least two different siderophore-mediated systems have been described so far in V. anguillarum. Most path- ogenic strains belonging to serotype O1 possess a system that is encoded by the 65-kb plasmid pJM1, which harbors genes for the synthesis and utilization of the catecholate-type siderophore anguibactin (2). 9,10 How- ever, serotype O2 strains and some plasmidless serotype O1 strains produce a siderophore, 11a given the trivial name of vanchrobactin (1), encoded by chromosomal genes and that is biologically unrelated to the anguibac- tin-mediated system. 11 The structure of vanchrobactin is still not determined, since attempts to reveal its complete structure have been hindered by problems associated with its purification in sufficient quantities and decom- position during isolation. In this letter, we wish to present the isolation, and the planar structural characterization of the mentioned siderophore vanchrobactin (1). 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.07.104 * Corresponding author. Tel.: +34 981 167000; fax: +34 981 167065; e-mail addresses: jaimer@udc.es; carlosjg@udc.es Tetrahedron Letters 47 (2006) 7113–7116