A gut-derived produces the novel nisin variant designated nisin G and inhibits in a model of the human distal colon microbiome.

is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-. activity revealed DPC6487 as a strain of interest. Whole-genome sequencing of DPC6487 identified a nisin operon with a novel structural variant designated nisin G. The structural nisin G peptide differs from the prototypical nisin A with respect to seven amino acids (Ile4Tyr, Ala15Val, Gly18Ala, Asn20His, Met21Leu, His27Asn, and His31Ile), including differences that have not previously been associated with a natural nisin variant. The nisin G gene cluster consists of with transposases encoded between the nisin G structural gene () and , notably lacking an equivalent to the immunity determinant. DPC6487 exhibited a narrower spectrum of activity compared to the nisin A-producing NZ9700. Nisin G-producing DPC6487 demonstrated the ability to control DSM15643 in an model colonic environment while exerting minimal impact on the surrounding microbiota. The production of this bacteriocin by a gut-derived , its narrow-spectrum activity, and its anti- activity in a model colonic environment indicates that this strain merits further attention with a view to harnessing its probiotic potential.IMPORTANCE is a human pathogen associated with intestinal conditions, including colorectal cancer, making it a potentially important therapeutic target. Bacteriocin-producing probiotic bacteria demonstrate the potential to target disease-associated taxa in the gut. A gut-derived strain DPC6487 was found to demonstrate anti-. activity, which was attributable to a gene encoding a novel nisin variant designated nisin G. Nisin G-producing DPC6487 demonstrated the ability to control an infection of in a simulated model of the human distal colon while exerting minimal impact on the surrounding microbiota. Here, we describe this nisin variant produced by , a species that is frequently a focus for probiotic development. The production of nisin G by a gut-derived , its narrow-spectrum activity against , and its anti-. activity in a model colonic environment warrants further research to determine its probiotic-related applications.