Mapping distal mutations allowed us to extend the enzyme’s operational life by 40-fold, a critical factor for long-term industrial cycles.
Pharmaceutical
Breaking IP barriers in API production
The Challenge: Navigating a Crowded Patent Landscape
Freedom-to-operate (FTO) can often be a hurdle in biocatalytic production. An API manufacturer approached Zymvol with a critical bottleneck: they required a novel R-selective transaminase for a key project, but the existing landscape was heavily restricted by over 10 different patents.
Without a novel, non-infringing enzymatic solution, the manufacturer faced the prospect of shutting down the project entirely.
The Solution
To overcome these IP barriers in biocatalysis, Zymvol implemented a two-phase computational approach combining Enzyme Discovery and Enzyme Optimization:
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- Enzyme Discovery
We began by computationally screening over 400,000 sequences, from which we managed to narrow down a selection of 16 top performers for laboratory validation. Out of the 16 sent to the lab, 6 enzyme hits were discovered. - Enzyme Optimization
Upon discovering 6 active hits from the initial 16, we set out to bridge the performance gap between the natural hits and the industrial biocatalysis requirements. Our team conducted 3 enzyme engineering rounds, testing only 300 mutants in the lab, a fraction of the effort required by traditional directed evolution methods.
- Enzyme Discovery
Results & Impact
- Outperforming commercial standards
The enzyme engineering campaign yielded a lead candidate that significantly surpassed existing benchmarks. Experimental validation confirmed that Zymvol’s top hit delivered 10x higher activity than the leading patented enzyme.
- Superior enantiomeric purity
Beyond activity, the precision of the engineered enzyme was significantly higher. While the leading patented enzyme achieved only 70% enantiomeric excess (e.e.), Zymvol’s best hit reached 99% e.e., meeting the stringent chiral purity standards required for high-quality API production.
- Revitalizing “dead-end” projects
By delivering a high-performing, novel enzyme in just 3 rounds of engineering, Zymvol enabled the client to bypass 10+ IP barriers and recover a project that was previously headed for cancellation.
Highlights
- 10x more activity
Our engineered hit outperformed the best patented enzyme available. - 99% ee
Achieved near-perfect stereoselectivity, compared to only 70% from existing patented solutions. - 3 rounds of engineering
A highly accelerated timeline, going from 400k sequences to a final optimized lead after testing only 300 mutants.
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