STRUCTURE AND BIOLOGICAL-ACTIVITY OF CHEMICALLY-MODIFIED NISIN-A SPECIES

Nisin, a 34-residue peptide bacteriocin, contains the less common, ami no acids lanthionine, beta-methyllanthionine, dehydroalanine (Dha), an d dehydrobutyrine (Dhb). Several chemically modified nisin A species w ere purified by reverse-phase HPLC and characterized by two-dimensiona l NMR and electrospray mass spectrometry. Five constituents, [2-hydrox y-Ala5]nisin, [Ile4-amide,pyruvyl-Leu6]des-Dha5-nisin, [Met(O)21]nisin . [Ser33]nisin, and nisin-(1-32)-peptide amide, were found in a commer cial nisin sample. A further species, [2-hydroxy-Ala5]nisin-(1-32)-pep tide amide, was obtained by freeze drying an acidic nisin solution. Th ese compounds are formed by chemical modification of nisin: the additi on of a water molecule to the dehydroalanine residues, which can lead to the cleavage of the polypeptide chain, or the oxidation of methioni ne residues. The 2-hydroxyalanine-containing products have a limited s tability; they are spontaneously converted into the corresponding des- dehydroalanine derivatives. The growth-inhibiting activity of the modi fied nisins towards different bacteria was determined. The 2-hydroxyal anine-containing species and the desdehydroalanine derivative show a s trong reduction in biological activity as compared to native nisin. [M et(O)21]nisin and [Ser33]nisin show moderate or no reduction in biolog ical activity.