Bifunctional Phosphoketolase-Phosphotransacetylase Fusion for Ethanol Yield

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Solution Overview

Problem

Current yeast-based ethanol production methods face challenges in maximizing ethanol yield while minimizing the production of undesirable by-products like acetate, which adversely affects alcohol production rates and yields.

Innovation Solution

Engineering yeast cells to produce a bifunctional phosphoketolase-phosphotransacetylase fusion polypeptide, which channels carbon flux towards ethanol production and reduces acetate production by converting fructose-6-P and/or xylulose-5-P to acetyl-CoA, thereby minimizing acetyl-phosphate accumulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If yeast metabolic pathways are modified to increase ethanol production, then ethanol yield is improved, but production of undesirable by-products such as acetate increases

Engineering Contradiction:
Improveethanol productionVSAvoidacetate production
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent combines phosphoketolase and phosphotransacetylase into a single bifunctional fusion polypeptide. This merging of two enzymatic functions into one protein allows coordinated catalysis of sequential reactions (fructose-6-phosphate to acetyl-CoA conversion), channeling carbon flux efficiently toward ethanol while minimizing acetate accumulation by preventing intermediate buildup

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The bifunctional polypeptide performs multiple enzymatic functions within a single protein structure. It possesses both phosphoketolase activity (cleaving fructose-6-phosphate) and phosphotransacetylase activity (converting acetyl-phosphate to acetyl-CoA), allowing one protein to execute a multi-step metabolic pathway that optimizes ethanol production while controlling by-product formation

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Productivity

If glycerol synthesis is reduced to improve ethanol yield, then ethanol production is improved, but other metabolic by-products such as acetate increase

Engineering Contradiction:
Improveethanol yieldVSAvoidacetate by-product
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by creating a specialized metabolic channel through the bifunctional enzyme that specifically handles acetyl-CoA production from fructose-6-phosphate. This localized enzymatic pathway ensures that carbon flux through this specific route is optimized for ethanol production while preventing the accumulation of acetyl-phosphate intermediates that would otherwise be converted to acetate

Inventive Principle:
Principle #3Local quality

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 increases ethanol yield by up to 5.9% and reduces acetate production by up to 80%, enhancing the efficiency of starch hydrolysis processes for alcohol production.

Implementation Method 1

bifunctional phosphoketolase-phosphotransacetylase fusion polypeptide, which channels carbon flux towards ethanol production and reduces acetate production by converting fructose-6-P and/or xylulose-5-P to acetyl-CoA

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

reduces acetate production by converting fructose-6-P and/or xylulose-5-P to acetyl-CoA, thereby minimizing acetyl-phosphate accumulation

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP3555295B1Bifunctional phosphoketolase-phosphotransacetylase fusion polypeptides
Publication Date: 2021.01.20 DANISCO US INC
  • EP3555295B1 patent drawingFigure 1
  • EP3555295B1 patent drawingFigure 2
  • EP3555295B1 patent drawingFigure 3

AI summary

Described are compositions and methods relating to bifunctional phosphoketolase-phosphotransacetylase fusion polypeptides and the use thereof in starch hydrolysis processes for alcohol production.