Therapeutic Application of Lantibiotics and Other Lanthipeptides: Old and New Findings

Abstract

Lanthipeptides are ribosomally synthesized and post translationally modified peptides, with modifications that are incorporated during biosynthesis by dedicated enzymes. Various modifications of the peptides are possible resulting in a highly diverse group of bioactive peptides that offer a potential reservoir for use in the fight against a plethora of diseases. Their activities range from the antimicrobial properties of lantibiotics, especially against antibiotic-resistant strains, to antiviral activity, immunomodulatory properties, antiallodynic effects and the potential to alleviate cystic fibrosis symptoms. Lanthipeptide biosynthetic genes are widespread within bacterial genomes providing a substantial repository for novel bioactive peptides. Using genome mining tools novel bioactive lanthipeptides can be identified and coupled with rapid screening and heterologous expression technologies the lanthipeptide drug discovery pipeline can be significantly sped up. Lanthipeptides represents a group of bioactive peptides that holds great potential as biotherapeutics, especially at a time when novel and more effective therapies are required. With this review we provide insight into the latest developments made towards the therapeutic applications and production of lanthipeptides, specifically looking at heterologous expression systems.

Mining and Biosynthesis of Bioactive Lanthipeptides From Microorganisms

“…Most of known lanthipeptides have antibacterial activity, especially against MDR strains, while some have antiviral, antitumor, antifungal, and immunomodulatory properties and some display the potential to alleviate cystic fibrosis symptoms. Other activities, such as morphogenetic and antinociceptive actions, have also been reported ( van Staden et al, 2021 ; Table 1 ).…”

“…Since the discovery of nisin in 1928, about a little more than one hundred of lanthipeptides have been reported from microorganisms, and they display complex and highly diverse structures and bioactivities ( Figure 1 ; van Staden et al, 2021 ).…”

“…These structural features determine the structural diversity and biological activity of lanthipeptides ( Biswas et al, 2017 ; van Staden et al, 2021 ; Figures 1 , 2 ).…”

“…It has been proposed that the target affinity of lanthipeptides is of great importance and crucial for their therapeutic potential ( van Staden et al, 2021 ).…”

“…Most of them possess multiple antibacterial mechanisms, endowing them with a high potential in the development of anti-infective drugs ( Mo et al, 2016 ). Nisin ( Figure 1 ), as the first-identified lanthipeptide containing 34 amino acid residues, has been used as a preservative food additive for over 60 years in more than 80 countries, but so far, few nisin-resistant bacteria have been found ( Mo et al, 2016 ; van Staden et al, 2021 ).…”