Transaminases (TAs) Engineering and Optimization Services

Transaminases (TAs) are pivotal biocatalysts essential for the green synthesis of Chiral Active Pharmaceutical Ingredients (APIs), notably in the high-efficiency production of amine intermediates for drugs like Sitagliptin. While traditional chemical methods often yield racemic mixtures, the industrial deployment of wild-type TAs faces limitations, including narrow substrate scope for non-natural amines, the high cost of the PLP cofactor, and poor activity in high-concentration or organic systems.

Our specialized enzyme engineering services and powerful technology platforms are designed to systematically overcome these constraints. Our capabilities focus on achieving: inversion or switching of enantioselectivity; enhanced thermal stability and tolerance to high substrate/organic solvent concentrations; and expansion of substrate promiscuity for novel amine synthesis. Consult with our experts to design a customized, high-value strategy that transforms your TA's performance for your unique industrial needs.

Challenges in Transaminase (TA) Industrial Deployment

The successful industrial application of TAs is limited by key factors, which our advanced services are specifically engineered to address:

• Limited Substrate Scope: Wild-type TAs often show high specificity, restricting their use with complex or sterically hindered non-natural amine precursors.
• Expensive Cofactor Management: The reaction requires the expensive PLP (Pyridoxal Phosphate) cofactor, necessitating efficient recycling or reducing consumption to ensure cost-effectiveness.
• Low Stability in Industrial Systems: TAs frequently exhibit poor activity and stability in the presence of organic solvents or high substrate/product concentrations common in scaled-up processes.
• Suboptimal/Undesired Stereoselectivity: The native enzyme may produce a racemic mixture or the incorrect enantiomer, requiring complete inversion of enantioselectivity.

Our platforms focus on addressing these molecular bottlenecks to deliver robust and efficient enzyme variants.

Engineering Focus: Achieving Industrial Performance

We apply integrated protein engineering strategies to enhance your target Transaminase (TA):

Stereoselectivity Inversion Service

             

We engineer the active site to invert or switch the chiral selectivity, aiming for enantiomeric excess e.e. > 99% for the desired S- or R-amine.

Stability and Tolerance Enhancement

Advanced engineering services to increase stability against thermal stress, organic solvents, and high substrate/product concentrations.

Substrate Promiscuity Expansion

We optimize substrate affinity and catalytic rate (kcat) to allow efficient conversion of non-natural, high-value amine and ketone substrates.

Cofactor Binding and Recycling

We offer cofactor engineering services to enhance PLP binding affinity, thereby reducing the required cofactor concentration for cost-effective synthesis.

Our experts are ready to apply these integrated capabilities to your specific TA candidate using Rational Design and Directed Evolution.

Cutting-Edge Technology Platforms

We leverage a suite of cutting-edge platforms to deliver highly functional enzyme variants:

High-Throughput Screening (HTS)

Platforms like Fluorescence-Activated Droplet Sorting (FADS) and microtiter plate screening enable rapid evaluation of millions of enzyme variants for desired activity and selectivity.

Computational Rational Design (CARD)

Using Computer-Aided Rational Design (CARD) services, we predict and prioritize key active site and allosteric mutations that optimize substrate fit and chiral bias.

Automated Evolution Technologies

Platforms such as Phage-Assisted Continuous Evolution (PACE) and Compartmentalized Self-Replication (CSR) accelerate the evolutionary process to generate optimized variants.

Comprehensive Kinetic Profiling

We offer full enzyme profiling services to accurately determine kinetic parameters ($K_m$, $V_{max}$) and operational stability under specific industrial conditions (e.g., in organic co-solvents).

Enzyme Immobilization and Formulation

Beyond molecular design, we offer services in stabilization and immobilization to ensure the engineered enzyme is ready for continuous-flow or reusable reactor systems at scale-up.

Partner with us to harness these platforms for your next biocatalysis breakthrough.

Project Flow: From Concept to Industrial Ready

Our enzyme optimization projects follow a flexible, milestone-driven workflow customized to your target goals:

• Consultation and Goal Definition: Initial discussion to define precise kcat, K_m, e.e., and stability targets for your TA.
• Design Strategy Proposal: We propose a tailored strategy, leveraging CARD and Directed Evolution, outlining the predicted timeframe and resources.
• Library Construction and Screening: We execute mutagenesis and employ HTS platforms to identify lead variants meeting intermediate milestones.
• Iterative Optimization: Successive rounds of evolution are performed under increasingly stringent conditions (e.g., high organic solvent content or product concentration) to build robustness.
• Final Deliverables: Delivery of the final enzyme variant, complete with detailed characterization and performance reports ready for your scale-up process.

Technical communication is maintained throughout the project. We encourage potential clients to initiate a consultation to discuss their specific TA requirements and explore how our technologies can achieve their desired yield and purity targets.

We provide comprehensive support, including:

• Detailed Kinetic Data, Enantiomeric Excess (e.e.), Solvent Tolerance, and Stability Reports.
• Consultation on process development and integration of the engineered enzyme into existing chemical or fermentation routes.
• Experimental reports including complete raw data on mutagenesis libraries, screening results, and chiral HPLC traces.