NRPSindependent

NRPSindependent is a term used in bioinformatics and genome mining to describe biosynthetic gene clusters (BGCs) that do not encode nonribosomal peptide synthetases (NRPS) and therefore produce metabolites via NRPS-independent pathways. In contrast to NRPS-containing clusters that assemble nonribosomal peptides through modular enzymes, NRPSindependent clusters rely on alternative enzymatic strategies to form their products. The label is commonly applied in annotation tools such as antiSMASH to help classify and compare diverse BGCs discovered in microbial genomes.

Most NRPSindependent BGCs are associated with siderophore biosynthesis, the microbial production of iron-chelating compounds that aid iron acquisition in iron-limited environments. These pathways typically employ enzymes outside the canonical NRPS family, including acyltransferases, oxidoreductases, and other ligases or tailoring enzymes, to construct hydroxamate, catecholate, or related siderophore backbones. Because the chemistry is distinct from NRPS-driven peptide assembly, NRPSindependent clusters expand the known diversity of natural products that microbes can produce for nutrient acquisition or ecological interactions.

Interpretation of NRPSindependent annotations should be cautious. The absence of NRPS genes in a cluster flagged as NRPSindependent may reflect true alternative biosynthetic routes, or it may indicate divergent or fragmentary gene predictions that obscure NRPS modules. Consequently, researchers often corroborate bioinformatic predictions with comparative genomics, experimental validation, and biochemical characterization.

In summary, NRPSindependent designations help categorize BGCs that manufacture specialized metabolites without NRPS modules, highlighting the diversity of microbial biosynthetic strategies and guiding further discovery efforts. See also NRPS, siderophore biosynthesis, and antiSMASH annotations.