Nosiheptide

Nosiheptide is a natural product thiopeptide antibiotic produced by certain Streptomyces species, most notably Streptomyces actuosus. It belongs to the thiopeptide class of sulfur-rich, highly modified macrocyclic peptides that typically contain multiple thiazole rings and other heterocycles around a central ring. The structure of nosiheptide includes several thiazole and oxazole rings within a macrocyclic core formed by extensive post-translational modifications.

Nosiheptide acts by inhibiting protein synthesis in bacteria. It binds to the 50S ribosomal subunit and interferes with translation, blocking translocation and elongation. This mechanism is shared with other thiopeptide antibiotics and contributes to potent activity against susceptible bacteria while limiting activity against many Gram-negative species due to uptake barriers.

In terms of antimicrobial spectrum, nosiheptide shows strong activity against Gram-positive organisms, including staphylococci and streptococci, with variable activity against some Gram-negative bacteria. It is used as a veterinary antibiotic, particularly as a feed additive to promote growth in poultry and sometimes other livestock, though regulatory status varies by country due to concerns about antimicrobial resistance.

Biosynthesis in producing strains involves a ribosomally synthesized precursor peptide that undergoes extensive post-translational modifications to install azole and thiazole rings, dehydroamino acids, and macrocyclization, yielding the mature thiopeptide. The responsible gene cluster encodes enzymes that drive this complex maturation, producing the characteristic nosiheptide scaffold.