Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 6 (4), 187-92

Bioengineering of the Model Lantibiotic Nisin

Affiliations
Review

Bioengineering of the Model Lantibiotic Nisin

Des Field et al. Bioengineered.

Abstract

The lantibiotics are a class of bacterially produced antimicrobial peptides (bacteriocins) that contain several unusual amino acids resulting from enzyme-mediated post-translational modifications. They exhibit high specific activity against Gram-positive targets, including many antibiotic-resistant pathogens, and consequently have been investigated with a view to their application as antimicrobials in both the food and medical arenas. Importantly, the gene-encoded nature of lantibiotics makes them more amenable to bioengineering strategies to further enhance their antimicrobial and physicochemical properties. However, although the bioengineering of lantibiotics has been underway for over 2 decades, significant progress has only been reported in recent years. This review charts recent developments with regard to the implementation of bioengineering strategies to enhance the functional characteristics of the prototypical and most studied lantibiotic nisin.

Keywords: antimicrobial peptide; bacteriocin; lantibiotic; mutagenesis; nisin; post-translational modification.

Figures

Figure 1.
Figure 1.
Post translational processing of nisin. Nisin is synthesized as a biologically inactive pre-peptide consisting of an N-terminal leader peptide attached to the C-terminal pro-peptide (A). Serine and threonine residues are dehydrated by NisB, forming dehydroalanine (Dha) and dehydrobutyrine (Dhb) respectively (B). NisC then couples nearby cysteine residues and the Dha and Dhb to form lanthionine (lan) and methyllanthionine (MeLan) rings, respectively (C). Modified nisin with the leader peptide still attached is subsequently transported via the dedicated ABC-type transporter NisT. Only after proteolytic cleavage of the N-terminal leader sequence, mediated by the extracellular serine protease NisP is the mature bioactive nisin peptide released (D).
Figure 2.
Figure 2.
Overview of enhanced bioengineered nisin derivatives. Structures of (A) nisin A and (B) nisin Z. Derivatives with increased specific activity as a result of the introduction of single amino acid substitutions are denoted by broken arrows/light green, or a combination of amino acid substitutions by braced/purple. Enhancement of physicochemical properties as a result of single amino acid substitutions are denoted by orange/broken line or by a combination of amino acid substitutions by braced/light blue. Post translational modifications are indicated as follows: Abu: 2-aminobutyric acid, Ala-S-Ala: lanthionine, Abu-S-Ala: 3-methyllanthionine) Dha: dehydroalanine, Dhb: dehydrobutyrine.

Similar articles

See all similar articles

Cited by 18 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback