Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800

Aims Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. Methods and Results This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. Conclusions Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. Significance and Impact of the Study Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

Automated summary

This study aimed to investigate the expression of natural nisin variants produced by non-GRAS strains in a GRAS host. It successfully demonstrated the heterologous production of three natural nisin variants by a genetically modified GRAS strain, showcasing the potential for expanding lantibiotic production and development for future biotherapeutics.