Case Study: Developing a High-Performance Enzyme for Industrial Biocatalysis
Our approach to an industrially viable enzyme
This case study shows how we took a holistic approach and combined technologies to provide a more efficient enzyme tailored to the needs of a specific industrial application.
Project highlights
- > 100,000+ sequences analyzed
- 36 novel enzymes from MetXtra™ tested experimentally
- >75% success rate for desired activity
- <100 enzymes from rational engineering tested experimentally
- >30% showed improved high-temperature activity
- Kilogram-scale enzyme production achieved
The challenge: rapid provision of an improved enzyme
Industrial biocatalysis often lacks enzymes enabling economically viable processes. A common case: a seemingly suitable enzyme has been identified for the desired biocatalytic reaction, but then it turns out that the enzyme candidate has serious drawbacks. This could be poor enzyme activity, insufficient thermostability or stereoselectivity, thus hindering industrial application.
While analyzing these challenges, an intriguing question often arises: Shall we engineer the current lead candidate or discover a novel enzyme with the desired properties?
Our solution: combining enzyme discovery & engineering
The goal was clear: improving the activity of an enzyme at elevated temperatures. This was necessary to enable an industrial application.
Our enzyme engineering experts applied our methodological portfolio for rational enzyme engineering and designed enzyme libraries to be tested. Less than 65 enzyme variants were tested in the first round of engineering to identify variants with improved activity at higher temperatures. The second and third round of engineering further enhanced the results with less than 100 tested enzyme variants in total.
Using the lead candidate as a starting point, MetXtra™ delivered more than 100,000 homologous sequences from public and proprietary metagenomic databases before narrowing the search using our bioinformatics toolbox to 36 experimental candidates.
In total, we characterized less than 100 enzyme variants resulting from the rational enzyme engineering approach and 36 novel enzymes for the enzyme discovery approach.
Efficient screening for improved enzymes was facilitated in complex assay setup. Multiple enzymes with high improvements were identified in both approaches and biocatalysis under application-relevant conditions verified these results.
Pilot-scale fermentation provided kilogram quantities of enzymes for further biocatalytic process development.
The outcome
The optimized enzyme met the customer's industrial performance criteria and enabled the subsequent development of a scalable biocatalytic process.
*This project has received funding from the European Union´s Horizon 2020 research an innovation program under grant agreement No 101000560.
