Biomolecular condensates can function as inherent catalysts
6 affiliations
- 1Department of Biomedical Engineering, Center for Biomolecular Condensates, James F. McKelvey School of Engineering Washington University in St. Louis, St. Louis, MO 63130, USA
- 2Department of Chemistry, Columbia University, New York, NY 10027, USA
- 3Department of Chemistry, Stanford University, Stanford, CA 94305, USA
- 4Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
- 5Department of Biomedical Engineering, Center for Biomolecular Condensates, James F. McKelvey School of Engineering Washington University in St. Louis, St. Louis, MO 63130, USA. Electronic address: [email protected]
- 6Department of Biomedical Engineering, Center for Biomolecular Condensates, James F. McKelvey School of Engineering Washington University in St. Louis, St. Louis, MO 63130, USA. Electronic address: [email protected]
Abstract
Biomolecular condensates possess distinct solvent environments. This has been postulated to affect biochemical activities. Here, we report the discovery of inherent catalytic functions of condensates formed by intrinsically disordered proteins. The proteins themselves lack any catalytic activities. The catalytic functions of condensates emerge as a consequence of phase separation-dependent mesoscale electrochemical microenvironments. Condensates can mediate the hydrolysis of diverse types of biologically relevant substrates. Through sequence design that enriches selective residues at condensate interfaces, interfacial electrochemical properties, such as interfacial electric field and water activity, are shown to control catalytic behaviors. Synthetic condensates in live cells exhibit hydrolytic activity, reshaping transcription profiles and activating gene circuits that depend on hydrolytic products. Together, these findings support a model that biomolecular condensates function as "condenzymes," contributing emergent biochemical functions in cells.
Related
- Long-range transport of biomolecular condensates by Marangoni effect
- Disulfide Crosslink Density is a Key Determinant in the Formation, Dynamics, and Maturation of Cysteine-rich Designer Biomolecular Condensates.
- e^-2 Threshold for Bistability in Non-equilibrium Sorting of Biomolecular Condensates
- Mesoscale Heterogeneity Shapes Molecular Selectivity and Transport in Biomolecular Condensates
- A unified intermediate-resolution framework for modeling biomolecular condensates at near-cellular complexity
BibTeX
@article{chen2026biomolecular,
title = {{Biomolecular condensates can function as inherent catalysts}},
author = {Michael W. Chen and Xiao Guo and Mina Farag and Naixin Qian and Xiaowei Song and Anton Z. Ni and Vicky Liu and Yu Xia and Yuefeng Ma and Leshan Yang and Wen Yu and Matthew R. King and Joonho Lee and Richard N. Zare and Wei Min and Rohit V. Pappu and Yifan Dai},
journal = {Molecular Cell},
year = {2026},
month = jul,
doi = {10.1016/j.molcel.2026.07.008},
url = {https://doi.org/10.1016/j.molcel.2026.07.008},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Biomolecular condensates can function as inherent catalysts
AU - Michael W. Chen
AU - Xiao Guo
AU - Mina Farag
AU - Naixin Qian
AU - Xiaowei Song
AU - Anton Z. Ni
AU - Vicky Liu
AU - Yu Xia
AU - Yuefeng Ma
AU - Leshan Yang
AU - Wen Yu
AU - Matthew R. King
AU - Joonho Lee
AU - Richard N. Zare
AU - Wei Min
AU - Rohit V. Pappu
AU - Yifan Dai
PY - 2026
DA - 2026/07/24
JO - Molecular Cell
DO - 10.1016/j.molcel.2026.07.008
UR - https://doi.org/10.1016/j.molcel.2026.07.008
AB - Biomolecular condensates possess distinct solvent environments. This has been postulated to affect biochemical activities. Here, we report the discovery of inherent catalytic functions of condensates formed by intrinsically disordered proteins. The proteins themselves lack any catalytic activities. The catalytic functions of condensates emerge as a consequence of phase separation-dependent mesoscale electrochemical microenvironments. Condensates can mediate the hydrolysis of diverse types of biologically relevant substrates. Through sequence design that enriches selective residues at condensate interfaces, interfacial electrochemical properties, such as interfacial electric field and water activity, are shown to control catalytic behaviors. Synthetic condensates in live cells exhibit hydrolytic activity, reshaping transcription profiles and activating gene circuits that depend on hydrolytic products. Together, these findings support a model that biomolecular condensates function as "condenzymes," contributing emergent biochemical functions in cells.
SN - 1097-2765
SN - 1097-4164
ER -