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Nosiheptide

Nosiheptide is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. It is classified, along with several others, as an e series thiopeptide characterized by a nitrogen containing, 6-membered heterocycle in a 2,3,5,6 substituted fashion central to multiple azoles (or azolines) and dehydroamino acids along with a macrocyclic core. Nosiheptide is constructed solely of proteinogenic amino acids and has ribosomal origin, making it a member of the ribosomally synthesized and posttranslationally modified peptide family of natural products. Thiopeptides such as nosiheptide have potent activity against various bacterial pathogens, primarily gram positive, including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci.

Nosiheptide consists of 5 thiazole rings, a central tetrasubstituted pyridine moiety, and a bicyclic macrocycle, which includes a modified amino acid (from tryptophan) external to the initial peptide translated from the gene encoding it. It is used as a feed additive in the growth of poultry and hogs to promote growth and general health, although it has not been applied in human medicines due to low water solubility and poor resorption from the gastrointestinal tract. Nosiheptide and other thiopeptide's mechanism of action stems from the tight binding on the 50S ribosomal subunit and inhibiting the activities of elongation factors, preventing protein synthesis.