Fermentation Temperature Shift for 1-Butanol Tolerance

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Solution Overview

Problem

Current methods for producing 1-butanol through fermentation are limited by the toxicity of the product to the microbial host, resulting in lower yields and higher production costs, with little known about the effect of temperature on tolerance to 1-butanol in recombinant microbial hosts.

Innovation Solution

A method involving a recombinant microbial host that undergoes a decrease in temperature during fermentation, increasing its tolerance to 1-butanol and enhancing production yields by seeding the host into a fermentation medium, growing it at an initial temperature, and then lowering the temperature to optimize 1-butanol production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fermentation is conducted at higher temperatures to maintain microbial growth rate, then productivity is improved, but the microbial host becomes more sensitive to 1-butanol toxicity

Engineering Contradiction:
Improve1-butanol production rateVSAvoid1-butanol toxicity to host
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The fermentation process dynamically adjusts temperature from an initial higher temperature (e.g., 37°C) during the growth phase to a lower temperature (e.g., 30°C or below) during the production phase. This dynamic temperature shift allows the microbial host to first grow rapidly at higher temperatures and then tolerate higher concentrations of 1-butanol at lower temperatures, resolving the contradiction between productivity and toxicity sensitivity

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the temperature parameter during the fermentation process to optimize both growth and production. By lowering the temperature after the growth phase, the microbial host's tolerance to 1-butanol increases, allowing higher production titers without compromising host viability

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the fermentation process is extended to increase 1-butanol titer, then productivity is improved, but host sensitivity to product toxicity increases

Engineering Contradiction:
Improve1-butanol production titerVSAvoidhost sensitivity to 1-butanol
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The temperature is lowered before the production phase begins, preparing the microbial host in advance to tolerate higher concentrations of 1-butanol. This preliminary temperature adjustment enables the fermentation to proceed longer and reach higher titers without the host becoming overly sensitive to product toxicity

Inventive Principle:
Principle #10Preliminary action

3Object-affected harmful factors

If temperature is lowered to increase 1-butanol tolerance, then host tolerance to product is improved, but fermentation rate decreases

Engineering Contradiction:
Improve1-butanol tolerance of hostVSAvoidfermentation rate
Core Design Contradiction:
Object-affected harmful factorsVSSpeed

Solution Approach 1:

The fermentation process is segmented into distinct phases: a growth phase at higher temperature (e.g., 37°C) for rapid microbial replication, and a production phase at lower temperature (e.g., 30°C or below) for high 1-butanol titer. This segmentation allows the system to optimize for speed during growth and for tolerance during production, resolving the contradiction between fermentation rate and product tolerance

Inventive Principle:
Principle #1Segmentation

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 higher 1-butanol production titers by reducing host sensitivity to the product, thereby increasing yields and potentially lowering production costs, while also offering an environmentally friendly alternative to petrochemical processes.

Implementation Method 1

a method for the production of 1-butanol by fermentation using a recombinant microbial host

Methodology Applied
Scientific EffectFermentation: Fermentation

Implementation Method 2

employing a decrease in temperature during fermentation that results in more robust tolerance of the production host to the 1-butanol product

Methodology Applied
Scientific EffectTemperature effect on microbial tolerance:

Data Source

PatentUS8426173B2Method for the production of 1-butanol
Publication Date: 2013.04.23 GEVO INC
  • US8426173B2 patent drawing

AI summary

A method for the production of 1-butanol by fermentation using a microbial production host is disclosed. The method employs a reduction in temperature during the fermentation process that results in a more robust tolerance of the production host to the butanol product.