Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

Area of Science:

• Microbiology
• Biotechnology
• Antimicrobial Resistance

Background:

• Rising antimicrobial resistance necessitates exploring novel antimicrobial compounds.
• Lantibiotics, like nisin, show promise, but their production is often limited by the producing organism's safety status.
• Investigating natural nisin variants from non-GRAS strains is crucial for expanding antimicrobial options.

Purpose of the Study:

• To express natural nisin variants (nisin H, J, P) from non-GRAS organisms in a Generally Recognized as Safe (GRAS) host.
• To assess the functionality of these variants within a heterologous expression system.
• To establish a foundation for the biotechnological production and diversification of lantibiotics.

Main Methods:

• Cloning of nisin A promoter and leader sequences fused to structural genes of nisin H, J, and P.
• Expression of these constructs in Lactococcus lactis NZ9800, a GRAS strain lacking endogenous nisin production.
• Induction of the nisin-controlled gene expression system to verify variant expression and activity.

Main Results:

• Successful heterologous expression of three natural nisin variants (nisin H, J, P) in Lactococcus lactis NZ9800.
• Demonstration that the host strain's nisin A machinery can process these variants.
• Confirmation of successful production of novel lantibiotics in a GRAS host.

Conclusions:

• This study represents the first successful heterologous production of these three nisin variants in a GRAS strain.
• The established system allows for the harnessing of lantibiotic production and expansion of their structural diversity.
• This work paves the way for developing novel lantibiotics as future biotherapeutics to combat antimicrobial resistance.