Structure, conformation and biological activity of a novel lipodepsipeptide from Pseudomonas corrugata: cormycin A1

Cationic lipodepsipeptides from Pseudomonas spp. have beencharacterized for their structural and antimicrobial properties.In the present study, the structure of a novel lipodepsipeptide,cormycin A, produced in culture by the tomato pathogen Pseudomonascorrugata was elucidated by combined protein chemistry,mass spectrometry and two-dimensional NMR procedures. Itspeptide moiety corresponds to L-Ser-D-Orn-L-Asn-D-Hse-L-His-L-aThr-Z-Dhb-L-Asp(3-OH)-L-Thr(4-Cl) [where Orn representsornithine, Hse is homoserine, aThr is allo-threonine, Z-Dhb is 2,3-dehydro-2-aminobutanoic acid, Asp(3-OH) is 3-hydroxyasparticacid and Thr(4-Cl) is 4-chlorothreonine], with the terminal carboxygroup closing a macrocyclic ring with the hydroxy groupof the N-terminal serine residue. This is, in turn, N-acylated by3,4-dihydroxy-esadecanoate. In aqueous solution, cormycin Ashowed a rather compact structure, being derived from an inwardorientation of some amino acid side chains and from the 'hairpinbent'conformation of the lipid, due to inter-residue interactionsinvolving its terminal part. Cormycin was significantly more activethan the other lipodepsipeptides from Pseudomonas spp., asdemonstrated by phytotoxicity and antibiosis assays, as well as byred-blood-cell lysis. Differences in biological activity were putativelyascribed to its weak positive net charge at neutral pH. Planarlipid membrane experiments showed step-like current transitions,suggesting that cormycin is able to form pores. This ability wasstrongly influenced by the phospholipid composition of the membraneand, in particular, by the presence of sterols. All of thesefindings suggest that cormycin derivatives could find promisingapplications, either as antifungal compounds for topical use or aspost-harvest biocontrol agents.