Genetically Modified Microorganisms Reducing Byproduct Formation

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Solution Overview

Problem

Biosynthetic pathways for producing chemicals like caprolactone, caprolactam, and adipic acid often result in unwanted byproducts that are toxic, affect product quality, and increase production costs and complexity, reducing efficiency and yield.

Innovation Solution

Genetically modified cells with specific enzyme modifications to decrease or increase enzyme activities, reducing byproduct formation and enhancing the production of target compounds such as hexamethylenediamine, levulinic acid, caprolactone, and adipic acid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional biosynthetic pathways are used to produce target chemicals, then production capability is achieved, but byproduct formation increases leading to reduced product purity and increased processing complexity

Engineering Contradiction:
Improveproduct purityVSAvoidbyproduct formation
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies the 'Taking out' principle by removing or eliminating specific enzymes (such as alcohol dehydrogenases, aldehyde dehydrogenases, and other oxidoreductases) from the biosynthetic pathway that are responsible for generating unwanted byproducts. This extraction of harmful enzymatic functions allows the pathway to produce target chemicals with significantly reduced byproduct formation, thereby improving product purity without compromising overall production capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs 'Parameter changes' by modifying the activity levels of specific enzymes through genetic engineering approaches. By altering enzyme expression levels, introducing mutations to reduce catalytic activity, or changing cofactor availability, the patent optimizes the biosynthetic pathway to minimize byproduct formation while maintaining target product synthesis, directly addressing the purity-byproduct contradiction

Inventive Principle:
Principle #35Parameter changes

2Productivity

If traditional biosynthetic pathways are used, then target product production is achieved, but production cost and process complexity increase due to downstream purification requirements

Engineering Contradiction:
Improveproduction efficiencyVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

By extracting and removing the enzymatic functions that generate byproducts, the patent simplifies the downstream purification process. The elimination of byproduct-forming enzymes results in a cleaner product stream that requires less complex separation and purification steps, thereby reducing both process complexity and associated costs while maintaining high productivity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies 'Discarding and recovering' by eliminating the generation of harmful byproducts at the source through enzyme removal. This prevents the accumulation of impurities that would otherwise require energy-intensive purification steps, waste treatment, and additional processing equipment, thereby reducing overall process complexity and operational costs

Inventive Principle:
Principle #34Discarding and recovering

3Adaptability or versatility

If non-naturally occurring microorganisms are used for biosynthesis, then target product capability is achieved, but undesired enzymatic activity produces byproducts

Engineering Contradiction:
Improvebiosynthetic capabilityVSAvoidundesired enzymatic activity
Core Design Contradiction:
Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent systematically identifies and removes specific enzymes from non-naturally occurring microorganisms that are responsible for undesired byproduct formation. By extracting these problematic enzymatic functions while preserving the core biosynthetic pathway, the patent maintains the adaptability and versatility of engineered microorganisms for producing target chemicals while eliminating their harmful byproduct-generating activities

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies 'Local quality' by making targeted modifications to specific enzymatic functions within the biosynthetic pathway rather than altering the entire organism. By locally adjusting or removing only the enzymes that produce byproducts while leaving other pathway components intact, the patent preserves the overall biosynthetic capability and adaptability of the microorganism while eliminating localized harmful activities

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS20240141397A1Microorganisms and methods for the production of biosynthesized target products having reduced levels of byproducts
Publication Date: 2024.05.02 GENOMATICA INC
  • US20240141397A1 patent drawing
  • US20240141397A1 patent drawing
  • US20240141397A1 patent drawing

AI summary

Provided herein are non-naturally occurring microbial organisms having biosynthetic pathways for production of target products and one or more genetic modifications that reduce a byproduct of the biosynthetic pathway. Compositions of target products from such cells and methods of using such cells are provided.