NRPSderived

NRPSderived refers to natural products produced by nonribosomal peptide synthetases (NRPS), a family of multi-enzyme assembly lines that synthesize peptides independently of ribosomes. These compounds span a wide range of bioactive classes, including antibiotics, siderophores, cyclic and lipophilic peptides, toxins, and immunosuppressants. NRPS-derived molecules often incorporate unusual amino acids and diverse chemical linkages, leading to structural features such as cyclization, prenylation, methylation, and glycosylation.

Biosynthesis and enzyme architecture are central to NRPS-derived chemistry. NRPS enzymes are organized into modules, with each module typically responsible for incorporating one amino acid. Within a module, the adenylation (A) domain selects and activates the amino acid, the peptidyl carrier protein (PCP, or thiolation) domain temporarily tethers it, and the condensation (C) domain catalyzes peptide bond formation. Optional domains can epimerize the amino acid (E) to its D-form, or introduce further modifications via tailoring domains such as methyltransferases or oxidoreductases. The sequence is usually terminated by a thioesterase (TE) domain that releases and often cyclizes the final product. Some NRPS systems feature iterative or mixed strategies rather than a strictly colinear module-per-amino-acid arrangement.

Significance and applications are broad. NRPS-derived products include many clinically important antibiotics (for example, penicillins, cephalosporins, vancomycin, daptomycin) and siderophores used by bacteria to acquire iron. Their modular nature has made them a focal point for bioengineering and combinatorial biosynthesis, aiming to create novel compounds by swapping or modifying modules and domains. Ongoing research seeks to better understand specificity, regulation, and the potential to generate new therapeutics.