Metabolically Engineered Microorganisms for 3-HP Production

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Solution Overview

Problem

Current microbial fermentation methods struggle to achieve commercially viable titers of 3-hydroxypropionic acid (3-HP) due to microbial inhibition by 3-HP concentrations and limitations in specific and volumetric productivity, necessitating improvements in microorganism engineering for enhanced production pathways.

Innovation Solution

Genetically modifying microorganisms to reduce enzymatic activity in the fatty acid synthase pathway and increase enzymatic activity in the malonyl-CoA reductase pathway, combined with modifications for increased tolerance to 3-HP, to produce 3-HP at higher specific and volumetric productivities, and converting it to acrylic acid for consumer products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microbial fermentation methods are used to produce 3-HP, then production can proceed with standard microorganisms, but the microbes are inhibited by 3-HP concentrations far below commercially viable titers, limiting productivity

Engineering Contradiction:
Improvespecific productivity and volumetric productivity of 3-HPVSAvoidmicrobial inhibition by 3-HP
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by genetically modifying microorganisms to alter their metabolic parameters - specifically reducing enzymatic activity in the fatty acid synthase pathway and increasing enzymatic activity in the malonyl-CoA reductase pathway. These parameter changes enable the microbes to tolerate higher 3-HP concentrations and achieve commercially viable productivities while converting malonyl-CoA to 3-HP

Inventive Principle:
Principle #35Parameter changes

2Productivity

If standard microbial systems are used for 3-HP production, then the process is simple to implement, but the net conversion to desired target chemical products remains insufficient for economically viable fermentation

Engineering Contradiction:
Improvenet conversion to 3-HPVSAvoidgenetic modification complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent implements parameter changes through targeted genetic modifications that alter key metabolic parameters in the microorganism. By modifying enzymatic activities in specific pathways (fatty acid synthase and malonyl-CoA reductase), the system achieves enhanced net conversion to 3-HP while maintaining a manageable level of genetic complexity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary action by pre-modifying the microorganisms with optimized metabolic pathways before fermentation. The genetic modifications are established in advance, allowing the microbes to efficiently convert malonyl-CoA to 3-HP during fermentation without requiring complex real-time adjustments

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

The approach results in significantly increased specific and volumetric productivities of 3-HP, enabling its efficient conversion to acrylic acid for use in consumer products, such as diapers, carpet, paint, and adhesives, with reduced reliance on petroleum-based carbon sources.

Implementation Method 1

The microorganism is genetically modified for increased enzymatic activity in the organism's malonyl-CoA reductase (mcr) pathway by introduction of a heterologous nucleic acid sequence coding for a polypeptide having mono-functional malonyl-CoA reductase activity

Methodology Applied
Scientific EffectEnzymatic activity: Enzyme

Implementation Method 2

combining a carbon source and a microorganism cell culture to produce 3-hydroxypropionic acid

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS10100342B2Method for producing 3-hydroxypropionic acid and other products
Publication Date: 2018.10.16 CARGILL INC
  • US10100342B2 patent drawing
  • US10100342B2 patent drawing
  • US10100342B2 patent drawing

AI summary

This invention relates to metabolically engineered microorganism strains, such as bacterial strains, in which there is an increased utilization of malonyl-CoA for production of a chemical product, which includes 3-hydroxypropionic acid.