Recombinant Yeast Formate Oxidation for Fermentation Robustness

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Solution Overview

Problem

Current yeast strains lack the ability to effectively oxidize formate to carbon dioxide during fermentation, leading to formic acid accumulation and reduced robustness, especially in the presence of stressors like lactic acid or bacterial contamination, which limits ethanol production and fermentation efficiency.

Innovation Solution

A recombinant yeast host cell is engineered with increased formate production and formate dehydrogenase activity, either through internal genetic modifications or by using a further yeast host cell with enhanced formate dehydrogenase activity, to maintain or increase fermentation yield and reduce glycerol production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If formate production is increased as an alternate electron sink to improve ethanol yield, then glycerol production is reduced, but formic acid accumulation occurs and reduces fermentation robustness

Engineering Contradiction:
Improveethanol yieldVSAvoidfermentation robustness
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent converts the harmful accumulation of formic acid into a beneficial process by introducing formate dehydrogenase activity that oxidizes formate to carbon dioxide. This transforms the toxic byproduct into a useful electron sink that maintains redox balance while eliminating the harmful acid accumulation, thereby preserving fermentation robustness while maintaining high ethanol yield

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the metabolic parameter by introducing formate dehydrogenase activity that alters the fate of formate. Instead of accumulating as formic acid, formate is oxidized to carbon dioxide, changing the metabolic pathway and eliminating the harmful effect while maintaining the beneficial electron sink function

Inventive Principle:
Principle #35Parameter changes

2Reliability

If formate dehydrogenase activity is introduced to oxidize formate and reduce formic acid accumulation, then fermentation robustness is improved, but additional genetic modification complexity is required

Engineering Contradiction:
Improvefermentation robustnessVSAvoidgenetic modification complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent enables the yeast cell to serve itself by introducing formate dehydrogenase activity that allows the cell to autonomously oxidize its own formate byproduct. This self-service mechanism eliminates the need for external intervention to manage formic acid accumulation, and the genetic modification is integrated into the cell's own metabolic machinery

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent merges the formate oxidation function with the yeast's existing metabolic network by introducing formate dehydrogenase activity that integrates with the cell's redox balance and energy metabolism. This combines multiple functions into a unified metabolic pathway that handles formate conversion while maintaining overall cellular homeostasis

Inventive Principle:
Principle #5Merging (Combining)

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 recombinant yeast host cell effectively oxidizes formate, reducing formic acid levels and enhancing ethanol production while maintaining or increasing fermentation yield, even under stressful conditions, thereby improving fermentation robustness and efficiency.

Implementation Method 1

formate dehydrogenase activity oxidizes formate to carbon dioxide

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

formate dehydrogenase activity

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

polypeptide having pyruvate formate lyase activity

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 4

fermenting glucose to ethanol

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS20220002661A1Modulation of formate oxidation by recombinant yeast host cell during fermentation
Publication Date: 2022.01.06 DANSTAR FERMENT AG
  • US20220002661A1 patent drawing
  • US20220002661A1 patent drawing
  • US20220002661A1 patent drawing

AI summary

The present disclosure concerns recombinant yeast host cells having a first genetic modification for increasing formate production, when compared to a corresponding native yeast host cell as well as a source of formate dehydrogenase activity. The source of formate can be an internal source of formate dehydrogenase activity and/or the recombinant yeast host call can be supplemented by an external source of formate dehydrogenase activity.