Biomolecular condensates mediate C-N bond formation.

Area of Science:

• Biochemistry
• Chemical Biology
• Metabolomics

Background:

• Biomolecular condensates are membrane-less organelles formed by intrinsically disordered proteins.
• Their function is primarily considered structural or regulatory, not catalytic.
• Nonenzymatic reductive amination is a key reaction for C-N bond formation in biological systems.

Purpose of the Study:

• To investigate the potential catalytic activity of biomolecular condensates.
• To explore the role of condensates in nonenzymatic reductive amination.
• To identify novel metabolites generated through condensate-mediated reactions.

Main Methods:

• In vitro experiments using purified intrinsically disordered proteins to form condensates.
• Assays to measure nonenzymatic reductive amination in the presence of condensates.
• Combinatorial metabolomics to identify reaction products.
• Metabolomic analysis in living cells.

Main Results:

• Biomolecular condensates spontaneously drive nonenzymatic reductive amination between amines and carbonyl compounds.
• Condensates facilitate the formation of imines and subsequent hydrogenation to alkylated amines, creating C-N bonds.
• Condensates generate novel metabolites via dimerization of amines with ketones/aldehydes.
• Condensate-mediated C-N bond formation was confirmed in living cells, leading to new metabolite synthesis and pathway regulation.

Conclusions:

• Biomolecular condensates possess inherent catalytic activity for nonenzymatic reductive amination.
• This function redefines the role of condensates beyond structural organization, highlighting their influence on metabolism.
• Condensates play a significant role in chemical homeostasis and biochemical regulation, with implications for both biological and prebiotic chemistry.