Biosynthesis, immunity, regulation, mode of action and engineering of the model lantibiotic nisin

Abstract

This review discusses the state-of-the-art in molecular research on the most prominent and widely applied lantibiotic, i.e., nisin. The developments in understanding its complex biosynthesis and mode of action are highlighted. Moreover, novel applications arising from engineering either nisin itself, or from the construction of totally novel dehydrated and/or lanthionine-containing peptides with desired bioactivities are described. Several challenges still exist in understanding the immunity system and the unique multiple reactions occurring on a single substrate molecule, carried out by the dehydratase NisB and the cyclization enzyme NisC. The recent elucidation of the 3-D structure of NisC forms the exciting beginning of further 3-D-structure determinations of the other biosynthetic enzymes, transporters and immunity proteins. Advances in achieving in vitro activities of lanthionine-forming enzymes will greatly enhance our understanding of the molecular characteristics of the biosynthesis process, opening up new avenues for developing unique and novel biocatalytic processes.

Quantifying Subpopulation Synergy for Antibiotic Combinations via Mechanism-Based Modeling and a Sequential Dosing Design

“…Static time-kill studies assessed nisin (4,8,32, and 128 mg/liter), amikacin (1,4,16, and 64 mg/liter), and linezolid (2, 8, and 32 mg/liter) in monotherapy.…”

“…The bacterial pellets were immediately resuspended in prewarmed broth containing no antibiotic (control), 8 or 16 mg/liter amikacin, or 8 or 32 mg/liter linezolid at approximately 1.75 h. In addition to the sequential combinations with pretreatment by nisin, simultaneous combinations also were studied, where the bacteria were simultaneously exposed to nisin plus amikacin or nisin plus linezolid throughout the whole experiment. The simultaneously dosed combinations were studied for selected informative combinations of nisin (8,16, and 32 mg/liter) with amikacin (4, 8, and 16 mg/ liter) or linezolid (2,8, and 32 mg/liter).…”

“…Due to its rapid killing of methicillin-resistant Staphylococcus aureus (MRSA) (16,17), nisin served as a probe drug.…”

Fundamental functionality: recent developments in understanding the structure–activity relationships of lantibiotic peptides

“…6 Nisin also shows considerable promise as a human therapeutic, especially for the treatment of drug-resistant bacterial infections. 7 As nisin SAR studies have been extensively reviewed, 4,6,7,11,12 we have chosen to limit this discussion to several recent studies.…”

Application Potential of Food Protein Modification

“…Some of these are also applied as food preservatives such as nisin, which is a potent antibacterial 34 amino acid peptide containing a number of uncommon amino acids. Nisin has been employed as an approved food preservative in cheese , fish, meat, and beverages (reviewed in Lubelski et al, 2008). Another known antimicrobial peptide is -poly-L-lysine which exhibits antimicrobial activity against bacteria and fungi and is used as a food preservative (reviewed in Hamano, 2011).…”