Retinoid Production via Microbial Cultivation and Lipophilic Stabilization

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Solution Overview

Problem

Current methods for producing retinoid are inefficient due to complex purification processes, generation of undesirable byproducts, and instability of chemically synthesized retinoid, which is prone to oxidation and degradation, limiting effective biotechnological production methods.

Innovation Solution

A method involving culturing microorganisms such as Escherichia coli with introduced genes for the MEP or MVA pathways, combined with a lipophilic substance like dodecane to stabilize and enhance retinoid production, allowing for efficient isolation and increased productivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical synthesis method is used to produce retinoid, then retinoid can be produced commercially available, but complicated purification processes are required and undesirable byproducts are generated

Engineering Contradiction:
Improveretinoid production efficiencyVSAvoidpurification process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts the retinoid production function from chemical synthesis and transfers it to a biological system (microorganism). By introducing the retinoid synthesis gene into a microorganism, the production process is relocated to a living cell that naturally performs the synthesis, thereby eliminating the need for complex chemical purification steps and byproduct removal processes.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses a microorganism as an intermediary between the genetic information (retinoid synthesis gene) and the final product (retinoid). The microorganism serves as a biological factory that converts simple substrates into retinoid through its metabolic pathways, simplifying the overall production process compared to direct chemical synthesis.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If chemical synthesis method is used to produce retinoid, then retinoid can be produced, but generation of undesirable byproducts occurs

Engineering Contradiction:
Improveretinoid productionVSAvoidundesirable byproducts
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the microorganism's natural metabolic capabilities into a benefit by directing its enzymatic pathways toward retinoid synthesis. Instead of dealing with harmful byproducts from chemical reactions, the biological system uses its inherent enzyme specificity to produce retinoid cleanly, transforming potential metabolic waste into desired product through genetic engineering.

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

Solution Approach 2:

The patent replaces the mechanical/chemical synthesis system with a biological system. The complex chemical reactions and purification mechanics are substituted by the microorganism's natural biochemical pathways, which inherently produce fewer byproducts and require simpler separation processes.

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

3Ease of manufacture

If retinoid is produced without stabilization measures, then production process is simple, but retinoid is easily oxidized and degraded by heat, oxygen and light

Engineering Contradiction:
Improveproduction process simplicityVSAvoidretinoid stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary stabilization measures by adding antioxidants to the culture medium before retinoid production begins. This preventive approach ensures that retinoid is protected from oxidation from the moment of synthesis, maintaining its stability throughout the production process without requiring complex post-production stabilization.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a protected environment for retinoid production by using antioxidants in the culture medium that scavenge reactive oxygen species and prevent oxidation. This establishes a chemically protective atmosphere within the biological system, shielding the sensitive retinoid from oxidative degradation during synthesis.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

4Productivity

If biotechnological method using metabolically transformed microorganisms is used, then retinoid production efficiency is improved, but complex gene introduction and culture conditions are required

Engineering Contradiction:
Improveretinoid production efficiencyVSAvoidgene introduction and culture complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent uses a microorganism that serves multiple functions: it acts as the genetic repository for the retinoid synthesis gene, the enzymatic factory for retinoid production, and the controlled environment for stable retinoid synthesis. This multi-functionality consolidates what would otherwise require separate systems into a single integrated biological platform.

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

Solution Approach 2:

The patent optimizes culture parameters such as temperature, pH, and antioxidant concentration to create ideal conditions for retinoid production. By carefully controlling these parameters, the system achieves high productivity while managing the complexity of biological culture through standardized, optimized conditions.

Inventive Principle:
Principle #35Parameter changes

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 method effectively produces retinoid with high efficiency, minimizing degradation and byproduct formation, and stabilizes the product, thereby improving productivity and purity.

Implementation Method 1

The microorganism may have natural or foreign genes introduced therein. The foreign gene may be a gene in association with production of retinoid such as at least one gene in an MEP or MVA path.

Methodology Applied
Scientific EffectMEP pathway:

Implementation Method 2

The foreign gene may be a gene in association with production of retinoid such as at least one gene in an MEP or MVA path.

Methodology Applied
Scientific EffectMVA pathway:

Implementation Method 3

culturing a microorganism having retinoid producing efficacy in a medium containing a lipophilic substance; and isolating retinoid from the lipophilic substance phase

Methodology Applied
Scientific EffectLipophilic stabilization:

Data Source

PatentUS9834794B2Method for producing retinoid from microorganism
Publication Date: 2017.12.05 INDUSTRYACADEMIC COOPERATION FOUNDATION GYEONGSANG NATIONAL UNIVERSITY
  • US9834794B2 patent drawing
  • US9834794B2 patent drawing
  • US9834794B2 patent drawing

AI summary

The present invention relates to a method for producing retinoid from a microorganism, and more specifically, to a method for effectively obtaining retinoid, which lacks stability, from a microorganism by cultivating the microorganism capable of producing retinoid in a medium containing a lipophilic substance, and separating retinoid from the lipophilic substance.