Technology at Codexis

Technology

Our technology

Our proprietary CodeEvolver® technology platform has the power to transform the performance of an enzyme, tailoring it for a specific application and process. Using powerful machine learning tools and sophisticated molecular, cellular, and bioanalytical workflows, we design and screen semi-rational libraries of thousands of variants in high throughput every 2-4 weeks on each project, sequencing every variant and correlating its sequence with its performance in a highly application-relevant screen.

Content-rich libraries screened under real-world conditions yield dense datasets, and multiple parameters can be optimized in parallel. The resulting evolved variants often have a combination of enhanced properties, such as increased activity, specificity, stability under desired conditions, or improved expression in the expression host. These enhanced properties provide differentiated technical performance in the target application and ROI in commercial deployment.

Our differentiation

Efficient, high-volume screening

We design semi-rational libraries by employing site-saturation mutagenesis at positions selected based on the target properties for improvement, which allows us to identify beneficial genetic diversity rapidly and comprehensively. Recombination of this diversity, guided by our proprietary bioinformatic tools, enables rapid progression through iterative rounds of evolution to navigate efficiently through sequence space. Therefore, we quickly reach effective library sizes greater than 1×1014 variants but only screen thousands of mostly active enzyme variants over a typical program.

Multiple properties targeted in parallel

We employ parallel screens for a broad set of properties: enzymatic activity, thermostability, pH stability, tolerance to organic solvent, serum stability, expression, and uptake into different cell types. This approach ensures that the final evolved enzyme delivers optimal application performance for multiple attributes, not just optimal assay performance. The ability of our bioinformatic tools to assess contributions from individual mutations in multiple contexts, and to suggest combinatorial designs that leverage multiple beneficial mutations in parallel, allows for efficient progression toward a no-compromise solution for a specific application. Further, the seamless integration of all components of our workflow means very short cycle times per round of evolution.

Rapid performance improvements

The combination of making larger improvements and having shorter cycle time per round, means that in the time other technologies may perform a few iterative rounds and meet a ten(s)-fold improvement over the starting enzyme, our technology can often perform many more iterative rounds and advance enzyme performance hundreds- or thousands-fold. In the real world, this can make the difference between achieving an economically viable enzyme product for the application, with a sensible investment, versus not achieving viable performance and/or spending too long and investing too much to get there.

Our application

Whether the enzyme is being targeted as a catalyst for production of a pharmaceutical or food ingredient, a component in a sequencing workflow, a functional enzyme in an industrial application or a biotherapeutic candidate, we apply the CodeEvolver® technology platform to design for a wide variety of applications, developing differentiated products in a diverse array of market.

Biotherapeutics

Biotherapeutics

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GI-stable oral biologics as potential PKU treatment

Treatment options for PKU are very limited. We engineered CDX-6114 to be an orally administered, GI-stable therapeutic enzyme that can potentially remove phenylalanine from the body before it reaches toxic levels. The program was licensed to Nestle Health Science and is currently in clinical trials.

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GI-stable oral biologics as potential PKU treatment

Treatment options for PKU are very limited. We engineered CDX-6114 to be an orally administered, GI-stable therapeutic enzyme that can potentially remove phenylalanine from the body before it reaches toxic levels. The program was licensed to Nestle Health Science and is currently in clinical trials.

Enhancing efficacy for Fabry Disease gene therapies

Fabry patients are in need of long-term efficacious treatments. In collaboration with Takeda our unique protein variant, CDX-6311, which was engineered for stability, activity, and reduced immunogenicity has shown promising results in pre-clinical studies when used as transgene for gene therapy.

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Enhancing efficacy for Fabry Disease gene therapies

Fabry patients are in need of long-term efficacious treatments. In collaboration with Takeda our unique protein variant, CDX-6311, which was engineered for stability, activity, and reduced immunogenicity has shown promising results in pre-clinical studies when used as transgene for gene therapy.

Life Science Tools

Life Science Tools

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Enabling novel Fully Enzymatic Synthesis™ through enzyme evolution

Chemical synthesis of oligonucleotides is challenged by length and purity limits. Codexis and Molecular Assemblies partnered to evolve a novel terminal deoxynucleotidyl transferase (TdT) enzyme to achieve high nucleotide incorporation rates, a key technology milestone for platform viability.

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Enabling novel Fully Enzymatic Synthesis™ through enzyme evolution

Chemical synthesis of oligonucleotides is challenged by length and purity limits. Codexis and Molecular Assemblies partnered to evolve a novel terminal deoxynucleotidyl transferase (TdT) enzyme to achieve high nucleotide incorporation rates, a key technology milestone for platform viability.

Evolving a more powerful enzyme for mRNA synthesis

mRNA-based therapies require the efficient manufacture and capping of synthetic mRNA. We developed Codex® HiCap RNA Polymerase to increase the yield of fully capped mRNA, while also reducing the amount of immunogenic double-stranded RNA byproduct generated.

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Evolving a more powerful enzyme for mRNA synthesis

mRNA-based therapies require the efficient manufacture and capping of synthetic mRNA. We developed Codex® HiCap RNA Polymerase to increase the yield of fully capped mRNA, while also reducing the amount of immunogenic double-stranded RNA byproduct generated.

Pharmaceutical Manufacturing

Pharmaceutical Manufacturing

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Doubling productivity in the manufacture of APIs for Merck

Improving API manufacturing processes is a challenge for pharmaceutical companies. Merck was faced with the prospect of building a second factory to meet the demand for its blockbuster drug Januvia®. A novel biocatalyst was developed to enable a significantly more efficient process, negating the need for a new facility.

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Doubling productivity in the manufacture of APIs for Merck

Improving API manufacturing processes is a challenge for pharmaceutical companies. Merck was faced with the prospect of building a second factory to meet the demand for its blockbuster drug Januvia®. A novel biocatalyst was developed to enable a significantly more efficient process, negating the need for a new facility.

Rapid scaling supports Pfizer in delivering a key treatment for COVID-19

As the world faced the worst pandemic in living memory, global pharmaceutical companies strove to rapidly discover and scale drug candidates which could address COVID-19. Codexis was able to support Pfizer in the synthesis of a critical intermediate for their COVID-antiviral, with a multi-ton production of enzyme to support tens of millions of treatments within a year from first clinical supply.

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Rapid scaling supports Pfizer in delivering a key treatment for COVID-19

As the world faced the worst pandemic in living memory, global pharmaceutical companies strove to rapidly discover and scale drug candidates which could address COVID-19. Codexis was able to support Pfizer in the synthesis of a critical intermediate for their COVID-antiviral, with a multi-ton production of enzyme to support tens of millions of treatments within a year from first clinical supply.

Food, Beverage & Nutrition

Food, Beverage & Nutrition

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A unique advantage in beverage production enabled by enzyme

A light-stable hop acid that can deliver consistent hop flavor characteristics and tastes is advantageous in beverage production. An engineered enzyme for Kalsec enabled a sustainable bioprocess, allowing for the use of clear glass bottles while maintaining a cleaner product label. 

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A unique advantage in beverage production enabled by enzyme

A light-stable hop acid that can deliver consistent hop flavor characteristics and tastes is advantageous in beverage production. An engineered enzyme for Kalsec enabled a sustainable bioprocess, allowing for the use of clear glass bottles while maintaining a cleaner product label. 

Achieving clean-label targets with lower production costs

Alternative sweetener manufacturers aim to lower production costs while maintaining taste and clean-label targets. Using enzymes tailored for specialized functions, Tate & Lyle was able to maximize the utilization of raw materials, improve yield, and minimize water and reagent use in two key sweetener product lines – DOLCIA® PRIMA Allulose and TASTEVA® M Stevia.

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Achieving clean-label targets with lower production costs

Alternative sweetener manufacturers aim to lower production costs while maintaining taste and clean-label targets. Using enzymes tailored for specialized functions, Tate & Lyle was able to maximize the utilization of raw materials, improve yield, and minimize water and reagent use in two key sweetener product lines – DOLCIA® PRIMA Allulose and TASTEVA® M Stevia.

Industrial Applications

Industrial Applications

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Sustainability service

Enzymes are the lynchpin of the circular economy. Mechanical recycling often yields plastic resins of low quality and restricted use, while enzymatic recycling has the potential to convert used consumer goods into pure starting materials for high value products. Other waste streams, including carbon dioxide itself, are captured and made available for storage and use with enzymes engineered to function under the extreme chemical and temperature conditions needed for industrial efficiency.

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Sustainability service

Enzymes are the lynchpin of the circular economy. Mechanical recycling often yields plastic resins of low quality and restricted use, while enzymatic recycling has the potential to convert used consumer goods into pure starting materials for high value products. Other waste streams, including carbon dioxide itself, are captured and made available for storage and use with enzymes engineered to function under the extreme chemical and temperature conditions needed for industrial efficiency.

Improved functionality

Consumer goods can be enhanced with enzyme actives and enzymatically produced ingredients to achieve better home care products, reduced carbon footprint and lifecycle impact, and clean labels. When engineered for a specific product, enzymes fit the formulation to provide full performance even with long supply chains and unpredictable home storage.

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Improved functionality

Consumer goods can be enhanced with enzyme actives and enzymatically produced ingredients to achieve better home care products, reduced carbon footprint and lifecycle impact, and clean labels. When engineered for a specific product, enzymes fit the formulation to provide full performance even with long supply chains and unpredictable home storage.

There are many steps to a healthier future.

Join us on our journey.