lipopeptides

Lipopeptides are a class of compounds composed of a lipid (fatty acid) tail covalently linked to a short or long peptide. They are amphipathic molecules that can be linear or cyclic and are produced by a range of organisms, most notably Bacillus species, as well as some fungi and other bacteria. The lipid component confers surface activity and facilitates interactions with biological membranes, underpinning many of their biological activities.

Structural diversity among lipopeptides is broad. Major categories include lipopeptide antibiotics, such as daptomycin and polymyxins, and lipopeptide biosurfactants, such as surfactin, iturin, and fengycin produced by Bacillus species, as well as rhamnolipids produced by Pseudomonas. Many lipopeptides are cyclic, formed by covalent bonds that close the peptide chain, though linear forms also occur. The lipid tail length and amino acid composition strongly influence function and target specificity.

Biosynthesis typically involves nonribosomal peptide synthetases (NRPS), which assemble the peptide independently of ribosomes, with the lipid tail attached through N-acylation or other covalent linkages. This modular assembly allows substantial structural diversity and bioactivity.

Mechanistically, antimicrobial lipopeptides disrupt cellular membranes. Daptomycin requires calcium to bind membranes and causes depolarization, leading to cell death. Polymyxins interact with lipopolysaccharides in Gram-negative membranes, increasing permeability. Surfactin acts as a powerful biosurfactant and can perturb membranes and reduce surface tension. Resistance can emerge via changes in membrane charge, reduced uptake, or enzymatic modification.

Applications of lipopeptides span medicine, agriculture, and industry. Clinically, certain lipopeptide antibiotics are used against difficult infections, while biosurfactant lipopeptides find use as environmentally friendly emulsifiers, detergents, and biocontrol agents.