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Directed Evolution and Enzyme Optimization

Natural enzymes are evolved by organisms to adapt to environmental conditions in nature. However, many natural enzymes exhibit limitations when applied under diverse industrial catalytic conditions, such as narrow substrate specificity, poor stability, and low catalytic concentrations. Therefore, natural enzymes must undergo directed modification according to specific industrial requirements to become practical biocatalysts.

Creative Biogene's Directed Evolution and Enzyme Optimization Service

Creative Biogene's Directed Evolution and Enzyme Optimization service harnesses the power of advanced artificial intelligence (AI) and deep learning technologies to revolutionize enzyme performance through sophisticated methodologies:

  • Enzyme Activity Prediction and Optimization

Employing machine learning and deep learning algorithms to predict enzyme activity and stability, particularly during mutation screening conducted via directed evolution. For example, Gaussian process models or other machine learning techniques are utilized to accurately forecast improvements in enzyme variants, thereby reducing the need for extensive experimental validation and lowering costs.

  • Enhancement of Stereoselectivity

Integrating machine learning with experimental design methodologies to optimize enzyme stereoselectivity. Techniques such as Adaptive Substitution Base Reshuffling Algorithm (ASRA) or similar approaches enable precise customization for specific substrates, leading to enhanced stereoselective outcomes.

  • Improvement in Solubility and Stability

Leveraging advanced machine learning models like SoluProt to predict enzyme solubility and stability, particularly under challenging conditions such as high temperatures and exposure to organic solvents. These models facilitate the identification of enzyme variants more likely to exhibit successful expression and stable performance.

  • Multi-Parameter Optimization

Applying machine learning strategies to efficiently optimize multiple aspects of enzyme functionality, including activity, selectivity, stability, and compatibility with diverse operational conditions and substrates.

  • Model Generalization and Applicability

Ensuring robustness across different enzyme classes and application scenarios by validating models extensively with comprehensive datasets. This approach ensures the effectiveness and reliability of solutions across a wide range of enzyme engineering projects.

This transformative capability not only accelerates the optimization process but also ensures that our solutions meet the highest standards of efficiency and efficacy in diverse industrial and pharmaceutical applications.

Service Process

1. AI Enzyme Structure Analysis

Utilizing advanced AI technologies to conduct in-depth analysis of enzyme structures, revealing critical functional characteristics and structural details through protein sequence and three-dimensional structure analysis.

2. AI-Assisted Mutation Design

Introducing AI technologies such as deep learning models and protein language models for comprehensive mutation analysis. These technologies predict the impact of mutations on enzyme function and stability, aiding in the design of mutant variants with superior performance.

3. Mutant Construction and Expression

Transferring designed mutant genes into expression hosts, such as bacteria or other expression systems, to ensure efficient protein expression for each mutant variant.

4. Functional Screening and Evaluation

Employing multiple testing methods in conjunction with AI predictions to screen and identify protein mutant variants with superior target performance. Confirmation of gene and protein sequences through sequencing validates AI predictions.

5. Iterative Optimization

Using the best-performing mutants as a basis for successive rounds of mutation and screening cycles. Continuous AI-driven optimization improves mutation design and screening processes until achieving the desired enzyme performance level.

6. Enzyme Performance Optimization

  • Enhanced Enzyme Activity: Improving catalytic efficiency and activity through optimized mutation design and screening processes.
  • Expanded Substrate Spectrum: Broadening enzyme substrate specificity to accommodate a wider range of substrates.
  • Improved Thermal Stability: Enhancing enzyme stability under high temperatures or other extreme conditions through structural optimization and mutation design.

Figure 1. Integrated Workflow: Machine Learning and AI Models Enhance NextGen Sequencing and Enzyme Screening.

Service Advantages

  • Efficient Screening: Utilizing unsupervised models, we efficiently screen protein mutant variants that adhere to evolutionary principles and natural constraints, significantly enhancing screening efficiency and positive rate. Our approach integrates both computational predictions and wet-lab experiments, ensuring robust validation of selected variants.
  • Precision Optimization: Combining advanced deep learning and machine learning technologies, we precisely predict enzyme activity and stability, providing accurate optimization strategies. Our methods are bolstered by comprehensive wet-lab experiments, validating predictions in real-world conditions.
  • Diverse Applications: Our services span a broad spectrum from industrial enzymes to pharmaceutical enzymes, meeting diverse client needs across various sectors with tailored solutions backed by rigorous wet-lab validations.
  • Advanced Technology Platform: Creative Biogene boasts state-of-the-art laboratory facilities and technical platforms, offering end-to-end services from gene synthesis, site-directed mutagenesis, and expression purification, to rigorous functional testing that includes both computational modeling and experimental validation.
  • Experienced Team: With an experienced team of scientists proficient in directed evolution and enzyme engineering, we provide clients with professional technical support and innovative solutions, integrating computational insights with practical wet-lab expertise to achieve optimal enzyme performance.

Experience the transformative power of Creative Biogene's Directed Evolution and Enzyme Optimization service, where advanced AI technologies sculpt bio-catalysts to unprecedented levels of performance, propelling industrial and pharmaceutical innovations to new heights of efficiency and excellence.

* For research use only. Not intended for any clinical use.
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