Recombinant Microorganism Fermentation Phase Control
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Solution Overview
Problem
Current methods for producing butanol through recombinant microorganisms face challenges in optimizing the butanol biosynthetic pathway and fermentation process, leading to limitations in biomass production, increased timing of propagation and production phases, and inefficient butanol yield.
Innovation Solution
The development of processes to produce improved cell cultures by providing recombinant microorganisms with an engineered butanol biosynthetic pathway, where the pathway is minimally or not activated initially, and then grown under adaptive conditions to increase pathway activation, optimizing biomass production and reducing the timing of fermentation phases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If the butanol biosynthetic pathway is activated early in fermentation, then butanol production starts earlier, but biomass production is reduced and cell growth is limited
Solution Approach 1:
The fermentation process is divided into distinct phases: a growth phase where the butanol pathway is repressed to maximize biomass accumulation, followed by a production phase where the pathway is activated for butanol synthesis. This temporal segmentation resolves the contradiction by separating the conflicting requirements of biomass production and butanol production into different time periods.
Solution Approach 2:
The system performs preliminary biomass accumulation during the growth phase before activating butanol production. By pre-building up cell mass when the pathway is repressed, the system ensures sufficient biomass is available before committing resources to butanol synthesis, thereby avoiding the trade-off between early production and biomass formation.
2Productivity
If the butanol biosynthetic pathway is highly active, then butanol productivity increases, but inhibitory intermediates accumulate and limit growth rate
Solution Approach 1:
The system dynamically controls pathway activation through phase-dependent regulation. During the growth phase, the butanol pathway is repressed to maintain healthy growth rates. During the production phase, the pathway is activated to maximize butanol productivity. This dynamic switching resolves the contradiction by adjusting pathway activity according to the physiological state and process stage.
Solution Approach 2:
The system maintains continuous useful action by ensuring seamless transition from growth to production phases. The regulatory mechanisms ensure that as biomass accumulates during the growth phase, the conditions naturally lead to pathway activation and butanol production, maintaining continuous productive activity without interruption or harmful intermediate accumulation.
3Quantity of substance
If the fermentation process is extended to maximize biomass, then butanol yield increases, but the timing of propagation and production phases increases
Solution Approach 1:
The system changes key parameters through phase transitions: during the growth phase, parameters favor biomass accumulation (repressed pathway, optimized growth conditions), while during the production phase, parameters shift to favor butanol synthesis (activated pathway, adjusted metabolic flux). This parameter switching enables high butanol yield without excessive propagation time by concentrating production activity in the optimized 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 results in increased biomass production, reduced fermentation time, enhanced butanol yield, and increased butanol productivity, while minimizing the production of inhibitory products, thereby achieving economical and efficient butanol production.
Implementation Method 1
the fermentative production of butanol and isomers thereof
Implementation Method 2
engineered butanol biosynthetic pathway
Data Source
AI summary
Provided herein are processes for producing an improved culture of cells comprising an engineered butanol biosynthetic pathway. The processes comprise (a) providing a cell culture of recombinant microorganisms comprising an engineered butanol biosynthetic pathway, wherein the engineered butanol biosynthetic pathway is minimal or not activated; and (b) growing the culture of recombinant microorganisms under adaptive conditions whereby pathway activation is increased to produce an improved cell culture and whereby the improved cell culture is capable of continuing to grow in fermentation.