Standing the heat: strategies shaping sustainable bioprocesses
Oeiras, 5th September 2025
In the current environmental crisis, adopting environmentally responsible bioprocesses is more important than ever. Enzymes play a central role in this effort, as they can significantly enhance the efficiency of industrial processes, making them cleaner, safer, and more resource-efficient. However, the limited stability of many enzymes often constrains their performance, creating a significant bottleneck to fully realizing their industrial potential. Therefore, advancing enzyme robustness and functionality is critical for enabling truly sustainable and eco-friendly industrial practices.
A team from ITQB NOVA’s Microbial & Enzyme Technology Lab, in collaboration with Laura Masgrau, a Professor from the Universitat Autònoma de Barcelona, has successfully stabilized enzymes at high temperatures using computational engineering tools. These tools introduce targeted mutations that modulate the enzyme’s structure and dynamics. Their findings, recently published in ACS Catalysis, not only reveal promising strategies to enhance enzyme performance and expand the impact of greener industrial processes but also uncover a previously unrecognized molecular fingerprint of stabilization.
The enzymes engineered by the ITQB NOVA team exhibited remarkable increases in stability at high temperatures. “The optimal temperatures of these enzymes rose nearly 40 °C, and their melting temperatures reached 72 °C and 83 °C, compared to 62 °C for the originals, whereas half-lives at 60 °C increased from 1 to 20 h. Importantly, these gains did not compromise their activity,” says Carolina Ferro Rodrigues, PhD student at ITQB NOVA and co-lead author of the study. Despite these advances, enzyme stability remains a complex phenomenon, influenced by multiple factors that are still poorly understood. According to Patrícia Borges, co-corresponding author, the group’s innovation lies in “highlighting the dynamic connectivity as a potential signature of thermostability, one that remains hidden in conventional static structural analysis, offering insight beyond the traditional rigidity-focused view.”
“This work opens up new possibilities in computer-based protein design by potentially integrating new concepts of dynamic network communication to guide enzyme design,” explains Lígia Martins, Principal Investigator of the lab. “While further studies are needed to understand the underlying mechanisms fully, our findings provide a promising new direction for creating enzymes that are more robust and better suited for industrial applications,” she adds.
Original paper:
ACS Publications | https://pubs.acs.org/doi/10.1021/acscatal.5c03333?fig=fig5&ref=pdf
Network Dynamics as Fingerprints of Thermostability in an In Silico-Engineered DyP-Type Peroxidase
Carolina F. Rodrigues, Diogo Silva, Constança Lorena, Patrícia T. Borges, Laura Masgrau, Lígia O. Martins
