nonribosomal

Nonribosomal describes biological processes or products that are not produced by the ribosome. In biochemistry, the term is most commonly applied to nonribosomal peptides (NRPs), a diverse class of peptides synthesized by dedicated enzyme systems known as nonribosomal peptide synthetases (NRPSs). Unlike ribosomal peptides, NRPs are assembled from amino acids by enzymatic assembly lines and frequently incorporate unusual amino acids and other moieties, yielding extensive chemical diversity and often potent biological activity.

NRPSs are large, multimodular enzymes in which each module typically selects and incorporates a specific amino acid. Core domains include an adenylation (A) domain for substrate activation, a peptidyl carrier protein (PCP, or thiolation) domain that tethers intermediates via a thioester, and a condensation (C) domain that forms peptide bonds. Additional domains can epimerize, methylate, or otherwise modify substrates; a thioesterase (TE) domain at the end often releases and cyclizes the final product. The resulting NRPs can be linear or cyclic and may feature nonstandard bonds or cross-links.

Nonribosomal peptides are notable for their medicinal and ecological roles. They include many antibiotics, siderophores, immunosuppressants, and toxins. Classic examples include penicillin and related beta-lactam antibiotics produced via NRPS pathways in fungi, vancomycin, and cyclosporin. NRPS gene clusters are a major focus of natural product discovery and bioengineering, enabling efforts to generate novel compounds through combinatorial biosynthesis. The nonribosomal paradigm is distinguished from ribosomal peptide synthesis, in which ribosomes translate mRNA templates; RiPPs (ribosomally synthesized and post-translationally modified peptides) represent another major class of nonribosomal-related peptide biochemistry.