Genetically Engineered Bacteria with Disrupted CODH Genes
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Solution Overview
Problem
Efficient production of fuels like ethanol and chemicals such as 2,3-butanediol from gaseous substrates like CO, CO2, and H2 is limited by diversion of carbon substrates into undesired byproducts and slow microorganism growth in existing microorganisms.
Innovation Solution
Genetically engineered carboxydotrophic acetogenic bacteria with decreased or eliminated carbon monoxide dehydrogenase (CODH) activity, specifically through disruptive mutations in CODH1 and/or CODH2 genes, and increased CODH/ACS activity, allowing for improved product profiles and growth characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If CODH1 and CODH2 genes are disrupted to decrease CODH activity, then ethanol and 2,3-butanediol production is improved, but acetate production increases as an undesired byproduct
Solution Approach 1:
The patent extracts and removes the harmful function of CODH1 and CODH2 enzymes by disrupting their genes, thereby eliminating the side reaction that produces acetate while preserving the desired fuel and chemical production pathways
Solution Approach 2:
The patent changes the activity parameter of CODH enzymes from active to inactive state through genetic disruption, fundamentally altering the metabolic flux distribution to favor ethanol and 2,3-butanediol production over acetate formation
2Manufacturing precision
If CODH1 and CODH2 genes are disrupted to improve product profile, then microorganism growth rate decreases and lag phase increases
Solution Approach 1:
The patent changes the metabolic state parameters of the microorganism by disrupting CODH genes, which fundamentally alters the growth kinetics and product formation characteristics to achieve superior product profiles despite initial growth adjustments
3Productivity
If carbon substrates are diverted into undesired byproducts, then fuel and chemical production efficiency decreases, but microorganism growth may be maintained
Solution Approach 1:
The patent extracts and eliminates the metabolic pathway responsible for carbon diversion to acetate by disrupting CODH genes, thereby channeling all carbon substrates toward the desired fuel and chemical production pathways
Solution Approach 2:
The patent discards the acetate production pathway by disabling CODH enzymes, thereby recovering and redirecting carbon substrates that would have been lost to byproducts into valuable fuel and chemical synthesis
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 genetically modified bacteria produce higher amounts of ethanol and 2,3-butanediol, have a shorter lag phase, and increased growth rate compared to parental bacteria, while reducing acetate production, thereby enhancing fermentation efficiency.
Implementation Method 1
Certain microorganisms can produce fuels, such as ethanol, and other chemicals, such as 2,3-butanediol, by fermentation of gaseous substrates comprising one or more of carbon monoxide (CO), carbon dioxide (CO2), and hydrogen (H2)
Implementation Method 2
carbon monoxide dehydrogenase (CODH) activity
Data Source
Figure 1(A)~1(D)
Figure 2A~2C
Figure 3A~4
AI summary
The invention provides genetically engineered microorganisms with altered carbon monoxide dehydrogenase (CODH) activity and methods related thereto. In particular, the invention provides a genetically engineered carboxydotrophic acetogenic bacterium having decreased or eliminated activity of CODH1 and/or CODH2. In certain embodiments, the bacterium may also have increased activity of CODH/ACS. The invention further provides a method for producing a product by culturing the bacterium in the presence of a gaseous substrate comprising one or more of carbon monoxide, carbon dioxide, and hydrogen.