Recombinant Microorganisms for Isoprenoid Production

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for obtaining mevalonate and isoprenoids are inefficient, often requiring complex organic synthesis or extraction from biological materials, which can be impractical due to low yields and the use of toxic solvents, limiting the practical use of these compounds.

Innovation Solution

Modulation of gene expression in recombinant microorganisms to enhance the activity of acetylating proteins and enzymes in the mevalonate-dependent biosynthetic pathway, increasing production of mevalonate, isoprene, isoprenoid precursors, and acetyl-CoA-derived products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional extraction methods are used to obtain isoprenoids from biological materials, then the compounds can be isolated, but the yields are low and toxic solvents are required

Engineering Contradiction:
Improveyield of isoprenoidVSAvoidtoxic solvents
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent replaces conventional chemical extraction methods with a biological production system using recombinant microorganisms. The mevalonate pathway enzymes are expressed in engineered microbes, allowing isoprenoid synthesis through controlled biochemical reactions rather than toxic chemical extraction, thereby eliminating harmful solvents while maintaining production capacity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent modifies the metabolic parameters of recombinant microorganisms by manipulating gene expression levels of key enzymes in the mevalonate pathway. Through controlling parameters such as enzyme activity, substrate concentration, and pathway flux, the system optimizes isoprenoid production yields without requiring toxic extraction solvents

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If organic synthesis is used to produce isoprenoids, then the compounds can be synthesized, but the process is complex and requires multiple steps

Engineering Contradiction:
Improveproduction of isoprenoidVSAvoidcomplexity of synthesis process
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent merges multiple synthetic steps into a single integrated biological system. By expressing a complete or partial mevalonate pathway in recombinant microorganisms, the system combines enzyme-catalyzed reactions that would otherwise require separate chemical synthesis steps, simplifying the overall process while maintaining product complexity

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The recombinant microorganism serves as a self-contained production system where the engineered metabolic pathway automatically converts substrates into isoprenoid products through intracellular enzyme catalysis, eliminating the need for complex external synthetic procedures and reducing process complexity

Inventive Principle:
Principle #25Self-service

3Quantity of substance

If conventional methods are used to obtain mevalonate and isoprenoids, then the compounds can be produced, but the yields are relatively low

Engineering Contradiction:
Improveyield of mevalonate and isoprenoidsVSAvoidproduction rate
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies partial action by expressing only the necessary enzymes of the mevalonate pathway in recombinant microorganisms, optimizing resource allocation to key rate-limiting steps. This targeted approach increases production efficiency and yield by concentrating metabolic flux through the engineered pathway rather than requiring complete biological material processing

Inventive Principle:
Principle #16Partial or excessive 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 increases the production of mevalonate and its derivatives, improving yields and reducing the need for toxic solvents, making these compounds more viable for commercial applications.

Implementation Method 1

The conversion of acetyl-CoA to mevalonate can be catalyzed by the thiolase, HMG-CoA synthase and the HMG-CoA reductase activities of the upper mevalonate-dependent biosynthetic pathway

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS11685937B2Recombinant microorganisms for the enhanced production of mevalonate, isoprene, isoprenoid precursors, isoprenoids, and acetyl-CoA-derived products
Publication Date: 2023.06.27 THE GOODYEAR TIRE & RUBBER CO
  • US11685937B2 patent drawing
  • US11685937B2 patent drawing
  • US11685937B2 patent drawing

AI summary

The invention features compositions and methods for the increased production of mevalonate, isoprene, isoprenoid precursor molecules, isoprenoids, and/or acetyl-CoA-derived products in recombinant microorganisms by engineering the microorganisms to comprise one or more acetylating proteins such that the expression and/or activity of the one or more acetylating proteins is modulated.