Probiotics are “live microorganisms which, when consumed in adequate amounts, confer a health benefit to the host”. A number of attributes are highly sought after among these microorganisms, including immunomodulation, epithelial barrier maintenance, competitive exclusion, production of short-chain fatty acids, and bile salt metabolism. Bacteriocin production is also generally regarded as a probiotic trait, but it can be argued that, in contrast to other traits, it is often considered a feature that is desirable, rather than a key probiotic trait. As such, the true potential of these antimicrobials has yet to be realised.

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. Here we describe Streptococcus agalactiae DPC7040, a human faecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a faecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.Nisin is a small peptide with antimicrobial activity against a wide range of pathogenic bacteria. It was originally sourced from a Lactococcus lactis subsp. lactis isolated from a dairy product 1 and is classified as a class I bacteriocin, as it is ribosomally synthesised and post-translationally modified 2 . Nisin has been studied extensively and has a wide range of applications in the food industry, biomedicine, veterinary and research fields 3-6 . It is approved as a food preservative by the Food and Agriculture Organization and is Generally Recognized As Safe (GRAS) by the United States Food and Drug Administration 4 .Structurally, nisin is classified as a lantibiotic because it contains lanthionine (Lan), an unusual amino acid formed by two alanine residues linked by a sulphur atom through their β-carbon 4 . Other unusual amino acids present in nisin are dehydroalanine (Dha), dehydrobutyrine (Dhb) and β-methyl-lanthionine 4 . Nisin activity and stability are closely related to its structure and can be altered by pH changes. Increasing pH results in decreasing activity as a consequence of alterations in structure, therefore, nisin is more stable at lower pH. Nisin is heat-stable and also exhibits high stability at low temperatures, which makes it suitable for freeze-storage 7 .Nisin has nine reported natural variants (Fig. 1, Table 1). Nisin A is the most studied nisin as it was the first one purified 8 . Nisin Z is considered the first natural variant of nisin A; it differs in the presence of an asparagine amino acid in position 27 instead of a histidine residue 9 . This substitution has very little effect on antimicrobial activity, thermal and pH stability compared to nisin A, but affects the solubility of the molecule, with nisin Z being more soluble at neutral pH 10 . A study of its distribution also revealed that nisin Z is more widespread than nisin A 10 . Nisin F, produced by L. lactis isolated from a fish gut, also has asparagine and valine in positions 21 and 30 11 . Nisin Q was identified in an environmental L. lactis isolate and differs from nisin A due to the presence of valine, leucine, asparagine and va...