Lipases Engineering Services for Chiral Resolution and Synthesis

Lipases (triacylglycerol acylhydrolases) are versatile hydrolases widely used in organic synthesis, notably for Prodrug Synthesis (Esterification) and Kinetic Resolution to obtain high-purity chiral molecules. They are highly valued for their ability to catalyze reactions in non-aqueous media. However, their industrial application faces major hurdles: low enantioselectivity for highly specific chiral resolution, and instability in the non-aqueous or supercritical CO₂ media that are often required for substrate solubility or green chemistry processes.

Our specialized enzyme engineering services are focused on overcoming these limitations through integrated Rational Design and Directed Evolution. Our core objectives include dramatically improving enantioselectivity for demanding chiral resolutions (targeting > 99.9% ee) and substantially enhancing the enzyme's stability and activity in harsh non-aqueous or low water activity media. Consult with our experts to design a customized strategy that transforms your lipase into a robust and highly selective industrial catalyst.

Challenges in Lipase Biocatalysis

The successful deployment of lipases in advanced chemical synthesis is limited by these critical factors:

• Low Enantioselectivity: While many lipases show some selectivity, achieving the extremely high enantiomeric excess (ee > 99.9%) required for pharmaceutical intermediates remains a major molecular challenge.
• Instability in Non-Aqueous Systems: The enzymes often lose structure and activity when exposed to the high concentrations of organic solvents or low water activity required for esterification or transesterification reactions.
• Suboptimal Activity: Low catalytic efficiency (k_cat) towards bulky, complex, or non-natural substrates reduces overall throughput and economic viability.
• Reusability: Loss of stability often impacts the enzyme's reusability, necessitating expensive immobilization or formulation steps.

Our engineering platforms are dedicated to resolving these complex molecular and operational bottlenecks.

Engineering Focus: Ultra-High Selectivity and Solvent Robustness

We apply integrated protein engineering strategies to enhance your target Lipase:

Ultra-High Enantioselectivity

             

We engineer the substrate binding pocket and catalytic triad to achieve extremely high selectivity (E > 500) for demanding chiral resolution applications.

Enhanced Solvent & Thermal Stability

Advanced stability engineering services to ensure high activity and longevity in non-aqueous media, high heat, and supercritical CO₂ systems.

Activity and Promiscuity Improvement

We optimize catalytic turnover and substrate specificity to handle bulky, non-natural, or difficult-to-hydrolyze ester substrates.

Immobilization-Ready Variants

We design lipase variants with enhanced surface properties and stability, making them ideal for subsequent immobilization services to maximize reusability.

Our experts are ready to apply these integrated capabilities to your specific lipase-catalyzed synthesis or resolution project.

Technology Platforms for Lipase Engineering

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

Computational Rational Design (CARD)

Using structural bioinformatics and molecular dynamics simulations, we predict and prioritize active site mutations that enhance enantioselectivity (E-value).

High-Throughput Screening (HTS)

We employ specialized colorimetric/fluorometric assays compatible with organic solvents and HTS methods to screen massive libraries for subtle increases in enantioselectivity.

Optimized Expression and Folding

Specialized expression and purification services focusing on obtaining fully folded and active lipases, often including chaperone co-expression or inclusion body refolding.

Comprehensive Enzyme Profiling

We offer full kinetic profiling, including E-value determination, solvent tolerance limits, and pH/temperature optima under industrial-relevant conditions.

Formulation and Stabilization

Beyond molecular design, we offer formulation development services to enhance the stability and shelf-life of the engineered lipase, particularly for non-aqueous applications.

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

Project Flow: Lipase Optimization Workflow

Our enzyme optimization projects follow a flexible, milestone-driven workflow:

• Consultation and Goal Definition: Initial discussion to define precise enantioselectivity (E-value > 500) and stability (% activity in specific solvent) targets.
• Design Strategy Proposal: We propose a tailored strategy involving Rational Design (focused on the lid and active site) and/or Directed Evolution, outlining the predicted timeframe.
• Library Construction and Screening: We execute targeted mutagenesis and employ HTS platforms to identify lead variants that meet intermediate selectivity and solvent tolerance milestones.
• Iterative Optimization & Profiling: Successive rounds of evolution are performed under increasingly challenging conditions (e.g., higher solvent content, elevated temperature) to build industrial robustness.
• Final Deliverables: Delivery of the final lipase variant along with detailed E-value, kinetic, stability, and reusability 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 lipase requirements and explore how our technologies can achieve their desired enantiopurity targets.

We provide comprehensive support, including:

• Detailed Kinetic Data, Enantioselectivity (E-value), Solvent Tolerance, and Thermal Stability Reports.
• Consultation on process development, including reactor design and integration of the engineered lipase.
• Experimental reports include complete raw data on mutagenesis libraries, screening results, and chiral HPLC traces.