Engineered Uridine Phosphorylase for Waste-Reduced Nucleoside Synthesis
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Solution Overview
Problem
The production of non-natural nucleoside analogs for cancer and viral infections is challenging due to chemical complexity and the generation of undesirable waste products, with standard chemical synthetic techniques often lacking suitable substrates and intermediates for industrial processes.
Innovation Solution
Engineered uridine phosphorylase enzymes with specific polypeptide sequences and substitutions are developed to catalyze the conversion of uridine and phosphate, facilitating the synthesis of non-natural nucleoside analogs efficiently and reducing chemical waste.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If standard chemical synthetic techniques are used to produce non-natural nucleoside analogs, then the production process can be established, but chemical waste is generated and substrates/intermediates may not be available for industrial conditions
Solution Approach 1:
The patent applies parameter changes by modifying amino acid residues at specific positions (e.g., positions 6, 7, 9, 14, 29, 31, 38, 40, 43, 47, 64, 73, 80, 86, 92, 97, 99, 103, 104, 105, 106, 110, 146, 147, 157, 167, 179, 181, 216, 226, 228, 231, 233, 235, 236, 237, 239, 240, 245) in the uridine phosphorylase polypeptide sequence to engineer enzymes with improved catalytic properties for industrial-scale production of nucleoside analogs
Solution Approach 2:
The patent replaces chemical synthetic techniques with biocatalytic methods using engineered uridine phosphorylase enzymes. This substitution eliminates the need for complex chemical substrates and intermediates while reducing chemical waste, as the enzymes catalyze the formation of nucleoside analogs through biological pathways under industrial process conditions
2Productivity
If chemical synthetic techniques are used, then production can proceed, but the chemical complexity poses challenges
Solution Approach 1:
The patent replaces complex chemical synthetic pathways with a single biocatalytic step using engineered uridine phosphorylase. This substitution simplifies the overall production process by eliminating multiple chemical synthesis steps, reagents, and purification operations while maintaining or enhancing productivity
Solution Approach 2:
The engineered uridine phosphorylase enzymes exhibit broad substrate specificity, enabling them to catalyze the formation of various nucleoside analogs from different substrates. This multi-functionality allows a single enzyme system to produce multiple pharmaceutical compounds, reducing the need for separate synthetic pathways for each analog
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The engineered uridine phosphorylases enhance the production of pharmaceutical compounds by providing efficient and waste-reducing methods for generating nucleoside analogs, addressing the limitations of traditional chemical synthesis.
Implementation Method 1
engineered uridine phosphorylase enzymes with specific polypeptide sequences and substitutions are developed to catalyze the conversion of uridine and phosphate
Data Source
AI summary
The present invention provides engineered uridine phosphorylase (UP) enzymes, polypeptides having UP activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing UP enzymes are also provided. The present invention further provides compositions comprising the UP enzymes and methods of using the engineered UP enzymes. The present invention finds particular use in the production of pharmaceutical compounds.