Corynebacterium glutamicum citrate synthase forms droplet-like condensates that depend directly on catalytic events, according to a study published in Nature Communications. The enzyme, abbreviated as CgCS, lacks typical intrinsically disordered sequences but condenses in relation to extracellular glutamate overproduction.
The research team found that CgCS condensates appear in actively growing bacterial cells and disperse once cells enter the stationary phase. When researchers tested CgCS variants lacking a functional catalytic residue, the proteins failed to form condensates. Across experiments, the degree of protein condensation tracked closely with catalytic activity.
Substrate interactions directly shaped this behavior. Oxaloacetate acted as a key factor governing condensate formation, while both oxaloacetate and acetyl-CoA modified the saturation concentration of CgCS depending on the presence of catalytic residues. The authors suggest that conformational heterogeneity generated during catalytic cycles drives enzyme condensation, offering a model for structured enzymes that lack disordered regions.
The project brought together researchers from the University of Tokyo's Graduate School of Agricultural and Life Sciences and Collaboration Research Institute for Innovative Microbiology, the Artificial Intelligence Research Center at AIST, and the RIKEN Center for Sustainable Resource Science. Authors included Makoto Nagaoka, Tomoshi Kameda, Kaito Kobayashi, Ayako Yoshida, Makoto Nishiyama, and Saori Kosono.
Kyoto University provided computational resources through the supercomputer at its Academic Center for Computing and Media Studies for molecular dynamics simulations. Microscopic imaging relied on a BZ-X810 fluorescence microscope provided by Hideaki Nojiri and Chiho Suzuki-Minakuchi. The paper was submitted on May 18, 2025, accepted on August 10, 2026, and officially published on August 20, 2026.
