subtilin

Subtilin is a ribosomally synthesized and post-translationally modified peptide (a lantibiotic) produced by certain strains of Bacillus subtilis. It belongs to class I lantibiotics and contains unusual amino acids such as lanthionine and methyllanthionine formed by enzymatic dehydration and cross-linking of serine/threonine and cysteine residues. The subtilin gene cluster encodes a precursor peptide with an N-terminal leader sequence; after modification by lantibiotic biosynthetic enzymes, the mature peptide is exported by a dedicated transporter and the leader is proteolytically cleaved to activate it.

Subtilin exhibits antibacterial activity primarily against Gram-positive bacteria, including Bacillus and Staphylococcus species, and to a lesser extent against certain Gram-negatives. Its mode of action involves binding to membrane-anchored lipid II, inhibiting peptidoglycan biosynthesis and, in some cases, forming pores that disrupt membrane integrity. This dual action leads to bactericidal effects in various model systems.

Spectrum and resistance: Subtilin's activity is generally narrower than broad-spectrum antibiotics and can be influenced by the target organism’s membrane composition and cell wall precursors. Resistance may arise through changes in lipid II, modification of the peptide target, or proteolytic degradation.

Applications and research: Subtilin has been studied as a potential biopreservative in food and as a prototype for new antimicrobials similar to nisin. However, commercial use has been limited by production yields, stability, and regulatory considerations. Ongoing research focuses on improving production, spectrum, and safety profiles, as well as understanding its structure–activity relationships.