Modified Spider Silk Proteins for Targeted Drug Coupling
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Solution Overview
Problem
Current methods for producing spider silk proteins face challenges in achieving sufficient protein yield and quality thread-assembly, particularly due to differences in codon usage between bacteria and spiders, and lack a satisfying technique for targeted coupling of substances to spider silk proteins.
Innovation Solution
Modified spider silk proteins are developed by incorporating amino acids with chemically specific side chains, such as cysteine and lysine, allowing for controlled coupling of substances like drugs and quantum dots, using a cloning system that enables precise assembly of DNA sequence modules and the use of specific TAGs for activation or modification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If spider silk proteins are produced using bacterial expression systems, then production scalability is improved, but protein yield and assembly quality deteriorate due to codon usage differences between bacteria and spiders
Solution Approach 1:
The patent applies codon optimization by changing the nucleotide sequence parameters of the spider silk protein genes to match bacterial codon usage preferences. This allows the same amino acid sequence to be expressed efficiently in bacterial systems, resolving the contradiction between scalability and protein quality by adapting the genetic code parameters rather than changing the protein structure.
Solution Approach 2:
The patent creates optimized copies of the original spider silk protein genes with modified codon sequences. These copied genes maintain the same amino acid sequence but use bacterial-preferred codons, enabling high-yield expression in E. coli while preserving the native protein's assembly properties and functional characteristics.
2Adaptability or versatility
If spider silk proteins are modified to enable targeted coupling of substances, then functional versatility is improved, but protein structure complexity increases
Solution Approach 1:
The patent introduces specific amino acid substitutions at predetermined local positions within the spider silk protein sequence. These localized modifications incorporate cysteine, lysine, or other chemically reactive residues at specific sites to enable targeted coupling of substances, while leaving the rest of the protein structure unchanged to maintain native assembly properties.
Solution Approach 2:
The patent divides the spider silk protein sequence into modular repeat units and introduces modifications at specific segment boundaries or within particular modules. This segmented approach allows independent optimization of different protein regions, enabling functional versatility through targeted coupling while maintaining the overall repetitive architecture that governs self-assembly.
Data Source
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AI summary
The present invention is directed to a method of modifying a spider silk protein and a spider silk protein obtainable by said method. The invention further pertains to a nucleic acid sequence coding for a modified spider silk protein, a vector containing said sequences and host cells transformed with this vector. The invention furthermore is directed to a pharmaceutical or cosmetical composition containing a modified spider silk protein as defined herein and the use of said modified sequences in various fields, in particular in the fields of medicine, cosmetics and technical applications.