A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity.

Area of Science:

• Microbiology
• Natural Product Chemistry
• Pharmacology

Background:

• Lanthipeptides are ribosomally synthesized peptides with complex post-translational modifications.
• Class III lanthipeptides are characterized by the presence of the triamino acid labionin.
• Bacterial cell wall inhibitors are a target for drug discovery.

Purpose of the Study:

• To discover and characterize novel lanthipeptides with potential therapeutic applications.
• To investigate the biological activity of a newly identified lanthipeptide, NAI-112.
• To evaluate the efficacy of NAI-112 in preclinical pain models.

Main Methods:

• Screening of bacterial strains for novel peptide production.
• Isolation and structural elucidation of the lanthipeptide NAI-112.
• Assessment of NAI-112 antibacterial activity.
• Evaluation of NAI-112 efficacy in mouse models of nociceptive pain (formalin test, chronic constriction injury test).

Main Results:

• Discovery of NAI-112, a 22-amino acid class III lanthipeptide from Actinoplanes sp.
• NAI-112 contains N-terminal labionin, C-terminal methyl-labionin, and a unique N-linked 6-deoxyhexose moiety on a tryptophan residue.
• NAI-112 exhibits weak antibacterial activity but demonstrates significant efficacy in reducing nociceptive pain in mouse models.

Conclusions:

• NAI-112 is a novel lanthipeptide with unique structural features, including a glycosyl moiety.
• NAI-112 shows promise as a non-antibiotic therapeutic agent for managing nociceptive pain.
• This discovery expands the known repertoire of lanthipeptides with analgesic properties.