moenomycin

Moenomycin is a natural product antibiotic produced by soil-dwelling actinomycetes, most commonly by Streptomyces species. It is a phosphoglycolipid composed of a long lipid tail linked to a pentasaccharide sugar moiety. This unique structure enables moenomycin to bind directly to the catalytic site of bacterial transglycosylases, enzymes that polymerize the glycan chains of peptidoglycan. By mimicking the natural donor substrate, moenomycin effectively blocks the transglycosylation step of cell wall synthesis, leading to rapid bacterial lysis in susceptible organisms.

Moenomycin displays potent in vitro activity against many Gram-positive bacteria and some Gram-negative species, but its clinical development has been limited by extremely poor pharmacokinetic properties, including poor oral bioavailability and inadequate systemic exposure. Consequently, moenomycin has not been approved for human therapy. In some countries, moenomycins have been used as feed additives in animal husbandry under brand names such as Flavomycin to promote growth, reflecting their activity in the gut without systemic administration. Regulatory status of antibiotic growth promoters varies by region.

Biosynthetically, moenomycins are produced by Streptomyces spp. via dedicated gene clusters that assemble the lipid, sugar, and linkage components as a discrete phosphoglycolipid antibiotic.

Moenomycin is of particular interest in antibiotic research because it targets the relatively underexploited transglycosylase step, a mechanism distinct from beta-lactams and other cell wall inhibitors. Resistance can arise through target modification or reduced uptake, though cross-resistance with other glycopeptide antibiotics is limited.