Success stories optimizing enzyme stability through expert analysis
Design, application, and techno-economic analysis
Proteins, the molecular workhorses of life, have found extensive applications across industries due to their remarkable catalytic and recognition capabilities. However, the gap between the natural functions of proteins and the demands of industrial processes often necessitates engineering interventions to enhance traits such as stability, efficiency, and substrate spectrum. At Nexco’s protein engineering and structural biology workflows we not only utilize modern AI tools but also apply decades of hands-on human expertise in protein design, engineering, computational modeling, and experimental characterization. Thus we are at the forefront of mastering protein design and engineering through all possible means.
In this blog post we bring to you a successful story illuminated by two recent papers that expose all the prowess behind optimizing enzyme stability for industrial use, including detailed analyses from the very initial design process itself to the characterization of the designed enzyme in the biophysics lab, its application in real industrial settings and conditions, and the quantification of its impact on costs, efficiency, and ecology. Usually, companies do not give away this amount of information, therefore these two papers are a very valuable resource and framework to illustrate all these aspects.
One of the articles presents the thermal stabilization of a bacterial phospholipase C through consensus sequence design, and the other presents how this stabilized enzyme allows for sustainable refining of vegetable oil while lowering costs and simplifying processes.
In more detail
Through retrieval of sequenced homologues from diverse sources followed by meticulous analysis and curation, the first work identified a subset of mutations for expression and characterization relative to a reference enzyme whose structure is deposited in the PDB and whose properties have been amply studied. Employing a non-natural protein derived from a consensus sequence, the authors achieved a significant enhancement in stability and activity. By comparing the stabilized mutant with natural variants bearing similar mutations, they pinpointed key sites responsible for the improvement. Notably, the stabilized version of the enzyme retained full activity even under the harsh conditions of oil degumming, making it a formidable candidate for industrial applications. And it was over 20 degrees more stable than the reference enzyme, and also more stable than commercial alternatives.
The second work, by the same set of authors, explains how traditional degumming methods using type C PLCs are environmentally friendly but face challenges with natural enzymes being inactive under the harsh conditions of oil refining plants. The synthetic enzyme obtained through consensus sequence design boasts superior thermal stability and catalytic properties, allowing for crude soybean oil degumming at the standard temperatures (very high to allow oil gum to flow) and residence time set by existing oil refining plants. The result is a remarkable increase in oil yield using around half of the recommended enzyme dose, translating to substantial cost savings. In more detail, a techno-economic analysis presented in the paper revealed that, for medium-sized plants, the stabilized enzyme reduces the overall cost of soybean oil enzymatic degumming by a staggering 58%. This not only streamlines the implementation of enzymatic technologies for oil producers but also carries the potential for billion-dollar annual benefits for the global economy.
Expert-based protein design at Nexco
This set of papers exemplifies very clearly the power of pushing for protein engineering, and of doing this not only via AI and other black-box methods but actually assisting the process with human experts who understand the underlying science. In this spirit, our expertise at Nexco goes beyond theoretical considerations, and we aim at translating cutting-edge research, frontier knowledge and state-of-the-art skills into tangible solutions with real-world applications. In particular for protein design and structural biology in general, the two papers presented here include experts who consult for us at Nexco.
As we look ahead, we remain at the forefront of revolutionizing enzyme engineering for industrial applications. Success stories like the one presented resonate in our work too, setting the stage for a future where enzyme-based biotechnology redefines efficiency, sustainability, and economic viability across diverse industries. Let’s meet to discuss your problems and how to tackle them through enzyme engineering, to contribute to a better, more efficient and sustainable world.
Here are the two papers discussed in this blog post. The techno-economic analysis paper came out first, although it actually presents the relevance of the design enzyme:
The protein design and characterization paper came out second:
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