Fermentation Process for 2,3-Butanediol Production

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Solution Overview

Problem

Current microbial fermentation processes for producing 2,3-butanediol from gaseous substrates, such as carbon monoxide, often result in 2,3-butanediol being a secondary product, with other products like ethanol being favored, making it economically unsustainable to increase 2,3-butanediol production effectively.

Innovation Solution

The method involves providing a gaseous substrate like CO, CO2, or H2 to a bioreactor with acetogenic carboxydotrophic microorganisms and inhibiting the flux of carbon to branched chain amino acids by adding compounds like 2-hydroxyisobutyric acid, which increases the production of 2,3-butanediol relative to other fermentation products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If microbial fermentation is used to produce 2,3-butanediol from gaseous substrates, then production of other products like ethanol is favored, but 2,3-butanediol becomes a secondary product with lower economic viability

Engineering Contradiction:
Improve2,3-butanediol productionVSAvoidethanol production
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by modifying the chemical environment through pH adjustment and addition of specific compounds (2-hydroxyisobutyric acid, 2-ketoisovalerate) to alter metabolic flux. These parameter changes shift the fermentation pathway preference from ethanol to 2,3-butanediol, resolving the contradiction by changing the chemical parameters that control product distribution

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses intermediary compounds (2-hydroxyisobutyric acid, 2-ketoisovalerate) as mediators that interact with the microbial metabolism to redirect carbon flow. These intermediaries act as metabolic modulators that suppress ethanol formation and promote 2,3-butanediol synthesis, effectively mediating the transition from one product dominance to another

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If carbohydrate feed stocks are used for 2,3-butanediol production, then production is economically sustainable, but cost is influenced by value as human food or animal feed

Engineering Contradiction:
Improveeconomic sustainabilityVSAvoidfeed stock cost
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent extracts the microorganism from its traditional carbohydrate-dependent metabolism and relocates it to utilize gaseous substrates (CO, CO2, H2). This extraction of the metabolic constraint allows production from non-food carbon sources, resolving the contradiction between economic sustainability and feed stock cost by removing the dependency on expensive carbohydrate feed stocks

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a copy of the fermentation capability that operates on alternative substrates. Instead of relying on the natural carbohydrate metabolism pathway, a modified fermentation system is created that copies the product synthesis capability while using gaseous substrates, thereby avoiding competition with food and feed markets

Inventive Principle:
Principle #26Copying

3Productivity

If flux of carbon to branched chain amino acids is inhibited, then production of 2,3-butanediol increases, but other fermentation products decrease

Engineering Contradiction:
Improve2,3-butanediol production rateVSAvoidother fermentation products
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by pre-adjusting the metabolic state through pH control and addition of inhibitory compounds before the main fermentation proceeds. This preliminary modification of the chemical environment pre-conditions the metabolic pathway to favor 2,3-butanediol production, resolving the contradiction by preparing the system in advance to channel carbon flux toward the desired product

Inventive Principle:
Principle #10Preliminary action

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 significantly enhances the production of 2,3-butanediol, achieving a ratio of 2,3-butanediol to ethanol of at least 10g/L per day with a desired ratio between 4:1 and 1:2, improving the economic viability of 2,3-butanediol production.

Implementation Method 1

2,3-butanediol can be produced by microbial fermentation of carbohydrate containing feedstock

Methodology Applied
Scientific EffectFermentation: Fermentation

Implementation Method 2

a culture of at least one acetogenic carboxydotrophic microorganism

Methodology Applied
Scientific EffectCarboxydotrophy:

Implementation Method 3

inhibiting the flux of carbon to branched chain amino acids by adding at least one compound to the liquid nutrient medium, wherein the at least one compound is selected from the group consisting of 2-hydroxyisobutyric acid (2-HIBA)

Methodology Applied
Scientific EffectMetabolic inhibition:

Data Source

PatentEP3047028B1A fermentation process
Publication Date: 2022.11.16 LANZATECH NZ INC
  • EP3047028B1 patent drawingFigure 1~2
  • EP3047028B1 patent drawingFigure 3~4
  • EP3047028B1 patent drawingFigure 5~6

AI summary

A methods for altering the metabolite profile of a fermentation, by increasing flux through acetolactate. The methods comprises increasing production of one or more products derived from acetolactate. Further provided is a method for increasing the production of 2,3-butandiol by microbial fermentation of gaseous substrates, the method comprising providing a compound which inhibits one or more enzymes which convert acetolactate to branched chain amino acids to the fermentation. The present invention further provides methods for increasing the production of 2,3-butandiol relative to other fermentation products such as ethanol and acetic acid.