Chimeric Cysteine-Rich Peptides for Cost-Effective Insect Control
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Solution Overview
Problem
Insects pose a significant threat to human health and food security by acting as disease vectors and damaging crops, with existing insecticides often being ineffective or costly.
Innovation Solution
Development of chimeric cysteine-rich proteins (CRPs) with specific disulfide bond scaffolds, produced using yeast expression systems, which are designed to target and inhibit insect pests.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing insecticides are used to control insect pests, then some level of pest control is achieved, but they are often ineffective or costly
Solution Approach 1:
The invention segments the insecticidal function into modular chimeric protein constructs composed of swap-compatible protein domains. Each domain can be independently optimized and recombined to create specialized insecticides targeting specific pest species or resistance mechanisms, reducing development costs through modular design rather than creating entirely new molecules each time.
Solution Approach 2:
The invention changes the fundamental parameter of insecticide structure by using chimeric cysteine-rich proteins with defined disulfide bond scaffolds instead of conventional small-molecule insecticides. This structural parameter change enables new modes of action and improved effectiveness while the yeast expression system addresses the cost parameter through efficient biological production.
2Reliability
If chimeric CRPs with specific disulfide bond scaffolds are developed to target insect pests, then potent insecticidal activity is achieved, but the complexity of protein structure and expression increases
Solution Approach 1:
The invention creates universal disulfide bond scaffold structures that can serve multiple insecticidal functions. The conserved cysteine-rich domains with specific disulfide bonding patterns (e.g., CXXC, CX2C, CX3C motifs) can be repeatedly used across different chimeric protein constructs, reducing the complexity burden by reusing proven structural modules rather than designing new complex structures each time.
Solution Approach 2:
The invention applies local quality by concentrating the essential insecticidal function in specific localized disulfide bond scaffold regions while allowing other parts of the chimeric protein to be more variable. The critical cysteine-rich domains with defined disulfide structures maintain strict structural quality, while swap-compatible regions can be diversified to target different pests, managing overall complexity through localized structural constraints.
3Productivity
If yeast expression systems are used to produce chimeric CRPs, then high yields are achieved, but the production process requires optimization for proper protein folding and disulfide bond formation
Solution Approach 1:
The invention enables self-service by designing chimeric CRPs with intrinsic disulfide bond formation capabilities that utilize the yeast cell's own oxidative environment. The cysteine-rich domains with appropriate spacing and motifs (CXXC, CX2C, CX3C) spontaneously form correct disulfide bonds during normal yeast protein processing, eliminating the need for external disulfide bond formation systems or complex post-translational modification protocols.
Solution Approach 2:
The invention applies preliminary action by pre-designing the chimeric protein sequences with optimized cysteine placement and disulfide bond motifs before expression. The swap-compatible protein domains are engineered in advance to contain the necessary structural features for correct folding and disulfide formation, allowing yeast to simply execute the predetermined folding pathway without requiring process optimization during production.
Data Source
AI summary
New insecticidal proteins and polynucleotides—and their expression in culture and plants—are disclosed. In addition, the present disclosure provides methods of producing the proteins and polynucleotides; new processes; new production techniques; new formulations; and new organisms. The present disclosure is also related to a novel type of protein named chimeric cysteine-rich insecticidal proteins (CRPs), comprising a disulfide bond scaffold, and subunits that are derived from swap-compatible proteins (SCPs). Here we describe: polynucleotides encoding chimeric CRPs: various formulations and combinations of both polynucleotides and peptides; and methods for using the same that are useful for the control of insects.