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CodeEvolver® Platform at Codexis

CodeEvolver® Platform

Powering Enzyme Engineering

Our proprietary CodeEvolver® technology platform has the power to revolutionize enzyme performance, tailoring it  for specific applications and processes. Leveraging advanced machine-learning tools with complex molecular, cellular, and bioanalytical workflows, we design, screen, and analyze libraries of thousands of enzyme variants in high throughput, sequencing each variant and correlating its sequence with its performance.

Content-rich libraries are screened under real-world conditions that yield dense datasets, with multiple parameters optimized in parallel. The resulting evolved variants often have a combination of enhanced properties, such as increased activity, specificity, stability, and expression. These enhanced properties translate into improved technical performance in the intended application and generate a return on investment in commercial settings.

Our differentiation

Efficient, high-volume screening

To design libraries, we target specific positions in the enzyme's genetic code that we have identified as crucial for improving its properties. This method enables us to identify beneficial genetic diversity rapidly and comprehensively. By using our proprietary bioinformatic tools to guide recombination of this diversity, we can efficiently navigate through the vast sequence space of enzyme variants. As a result, we can rapidly reach effective library sizes of over 1x1014 variants, but typically only screen a few thousand of the most active enzyme variants during each program iteration.

Multiple properties targeted in parallel

We use parallel screening methods to evaluate a broad set of enzyme properties, including enzymatic activity, thermostability, pH stability, organic solvent tolerance, serum stability, expression, and uptake into different cell types. By assessing multiple attributes simultaneously, we ensure that the final evolved enzyme delivers optimal application performance across a range of metrics, rather than just optimizing assay performance. Our bioinformatic tools can evaluate the contribution of individual mutations in different contexts and suggest combinatorial designs that leverage multiple beneficial mutations in parallel. This approach enables us to efficiently progress toward a no-compromise solution for specific applications. Additionally, our seamless workflow integration results in short cycle times per round of evolution, further streamlining the process.

Rapid performance improvements

Our technology's unique combination of making larger improvements and having shorter cycle times per round allows us to advance enzyme performance by hundreds or thousands of folds while other technologies may only achieve a ten-fold improvement after a few iterative rounds in the same amount of time. This significant performance improvement can make all the difference in the real world, as it can mean the difference between developing an economically viable enzyme product for a particular application with a reasonable investment, or failing to achieve viable performance and/or investing too much time and resources to get there.

Pharmaceutical Biocatalysis

The CodeEvolver® technology platform enables the discovery of biocatalysts for the manufacture of small molecule pharmaceuticals, with greatly improved traits including activity, selectivity, and stability. When combined into consecutive enzymatic conversions, the biocatalytic cascades can accomplish difficult chemistry under mild reaction conditions, with minimal waste generation and attractive economics. We currently have 18 commercial API programs, a further 18 in Phase II/III studies, three platform licenses, and over 50 programs in research and early clinical phases.

Life Sciences

Enzymes play a critical role in life science workflows. Using the CodeEvolver® technology platform, we have developed a novel engineered DNA ligase with superior ligation efficiency, and an RNA polymerase to produce quality mRNA at commercial scale. The CodeEvolver® technology platform underpins the key innovations behind the new Enzyme-Catalyzed Oligonucleotide Synthesis ECO SynthesisTM technology, which promises to disrupt existing phosphoramidite-based processes.

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