Biomolecular condensates mediate C-N bond formation

Abstract

We discover that biomolecular condensates, formed by intrinsically disordered proteins without inherent chemical activity, can spontaneously drive nonenzymatic reductive amination. These condensates facilitate reactions between amines and aldehydes or ketones, yielding imines, which are subsequently hydrogenated to form alkylated amines leading to C-N bond formation. Our experiments show that condensates modulate the reductive amination of diverse types of metabolite containing carbonyl groups. Using combinatorial metabolomics, we found that condensates generate previously unknown metabolites through the dimerization of natural amines with ketones and aldehydes. Metabolomics in living cells confirms that the ability of condensates in mediating C-N bond formation enables the synthesis of new metabolites and regulates cellular pathways. These findings uncover a previously unrecognized inherent function of biomolecular condensates, redefining their roles in metabolism. This further highlights the broader influence of condensates on chemical homeostasis and biochemical regulation in biological and prebiotic chemistry.