Case Study: Providing an enzyme that works in industrial biocatalysis

Case Study: Providing an enzyme that works in industrial biocatalysis

A dream team: Enzyme discovery & engineering

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.

Our approach to an industrially viable enzyme

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 this challenge to develop a tailored solution, an intriguing question arises: Shall we engineer the current lead candidate or discover a novel enzyme with the desired properties?

Combining enzyme discovery & engineering

Discover, create or both? It is the result that counts!

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.

Simultaneously, the lead candidate was used as the starting point for the discovery campaign. Inspired by nature’s diversity, our MetXtra™ technology platform explored the sequence space in public databases and our proprietary MetXtra™ metagenome database. Over 100.000 homologous sequences were identified before our discovery workflow progressively narrowed the sequence space to the most promising candidates. Ultimately, only 36 sequences had to be analyzed in the wet lab. The discovery campaign reported a success rate of >75% in desired activity and an impressive >30% in enhanced activity at higher temperatures.

In total, we characterized less than 100 enzyme variants resulting from the rational enzyme engineering approach and less than 40 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.

Technology Services: Enzymes & Proteins

A tailored enzyme that works in the application

We have combined expertise in technologies such as enzyme discovery and engineering to achieve optimal results. We optimized enzymes via rational design while simultaneously identifying novel candidates fulfilling the industrial criteria utilizing our MetXtra™ technology platform.

MetXtra™ provides access to novel enzymes and enables the tailored selection of those with the desired properties. Likewise, the rational optimization of lead candidates is enhanced through in silico methods. Whether the goal is to improve activity, thermostability, or stereoselectivity, sophisticated AI predictions and structural bioinformatics - including molecular dynamics simulations and docking studies - ensure effective and reliable workflows.

The MetXtra™ technology platform
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 this challenge to develop a tailored solution, an intriguing question arises: Shall we engineer the current lead candidate or discover a novel enzyme with the desired properties?

Our Solution

Combining enzyme discovery & engineering

Discover, create or both? It is the result that counts!

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.

Simultaneously, the lead candidate was used as the starting point for the discovery campaign. Inspired by nature’s diversity, our MetXtra™ technology platform explored the sequence space in public databases and our proprietary MetXtra™ metagenome database. Over 100.000 homologous sequences were identified before our discovery workflow progressively narrowed the sequence space to the most promising candidates. Ultimately, only 36 sequences had to be analyzed in the wet lab. The discovery campaign reported a success rate of >75% in desired activity and an impressive >30% in enhanced activity at higher temperatures.

In total, we characterized less than 100 enzyme variants resulting from the rational enzyme engineering approach and less than 40 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.

Technology Services: Enzymes & Proteins
Your Benefit

A tailored enzyme that works in the application

We have combined expertise in technologies such as enzyme discovery and engineering to achieve optimal results. We optimized enzymes via rational design while simultaneously identifying novel candidates fulfilling the industrial criteria utilizing our MetXtra™ technology platform.

MetXtra™ provides access to novel enzymes and enables the tailored selection of those with the desired properties. Likewise, the rational optimization of lead candidates is enhanced through in silico methods. Whether the goal is to improve activity, thermostability, or stereoselectivity, sophisticated AI predictions and structural bioinformatics - including molecular dynamics simulations and docking studies - ensure effective and reliable workflows.

The MetXtra™ technology platform

Enzyme discovery & engineering simultaneously

How can you benefit from this?

Identification of a tailored enzyme displaying the right properties is crucial for application. By collaborating with us, you can take advantage of both technologies simultaneously (enzyme discovery & engineering).

Enzyme engineering and discovery campaigns can be performed simultaneously, consecutively or independently tailored to your needs. We established multi-parameter screening methods implemented across the variety of our expression strains – not limited to E. coli.

An efficient screening for improved candidates can be facilitated even in a complex evaluation setup.

Which challenges does your biocatalytic process face?
how can we support you to reach your targets?

Let us jointly tailor your enzyme for industrial application. Contact us!