Engineered Cells with Regulated Protein Degradation for Metabolic Flux Control
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Solution Overview
Problem
Metabolic engineering faces challenges in reducing biomass production and feedstock costs, particularly when producing compounds like ethanol, butanol, and amino acids, as much of the feedstock is diverted into growth pathways rather than product synthesis, and expensive nutrients are required.
Innovation Solution
Engineered cells with proteins that include enzymatic functions connected to degradation sequences, allowing for regulated protein degradation upon addition or withdrawal of factors like chemicals or photons, which enhances the synthesis and secretion of desired products while minimizing biomass growth and feedstock usage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If feedstock is provided for microbial growth, then cell biomass increases, but product synthesis is reduced because much of the feedstock is channeled into growth pathways
Solution Approach 1:
The invention employs dynamic control of enzyme activity through regulated protein degradation. Proteins are equipped with degradation sequences that allow their levels to be dynamically adjusted by adding or withdrawing regulatory factors (chemicals, proteins, photons, temperature changes), enabling the system to shift between growth and product synthesis modes
Solution Approach 2:
The invention changes the parameter of protein stability by introducing degradation sequences. This allows controlled reduction of specific protein levels (such as catabolic enzymes or anabolic enzymes involved in biomass production) to redirect metabolic flux from growth pathways to product synthesis pathways
2Productivity
If expensive feedstock components are used to support growth, then cell growth is enhanced, but production cost increases
Solution Approach 1:
The invention extracts and removes specific proteins that are responsible for consuming expensive feedstock components. By introducing degradation sequences targeted at these proteins, the system eliminates their function, thereby stopping the consumption of expensive nutrients while maintaining cell viability and product synthesis
Solution Approach 2:
The invention creates short-lived protein versions with degradation sequences that can be rapidly removed when no longer needed. This allows the system to temporarily utilize proteins for growth when necessary, then quickly degrade them to eliminate expensive feedstock consumption during production phase
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
This approach enables cost-effective production of desired compounds by optimizing metabolic pathways, reducing feedstock costs, and enhancing product yield by controlling protein levels and metabolic flux.
Implementation Method 1
The cell contains one or more proteins that include an enzymatic function with an engineered connection to a sequence that can promote degradation of the protein
Data Source
AI summary
The invention features methods and compositions relating to cells that have been engineered to reduce or eliminate proteins having enzymatic activity that interfere with the expression of a metabolic product.