PHO84-Enhanced Yarrowia for Stable Retinoid Fermentation

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Solution Overview

Problem

Current methods for producing retinol through microbial fermentation have limited success in stabilizing and increasing the production of retinol, necessitating the development of a microorganism with enhanced PHO84 protein activity to improve retinoid production.

Innovation Solution

A Yarrowia sp. microorganism with increased PHO84 protein activity is engineered to enhance retinoid production by culturing it in a suitable medium, utilizing vectors and genetic modifications to introduce and express polynucleotides encoding PHO84 proteins with enhanced activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical synthesis methods are used for retinol production, then production capacity is maintained, but production stability and cost-effectiveness deteriorate

Engineering Contradiction:

Improveretinol production capacityVSAvoidproduction stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the PHO84 protein through site-directed mutagenesis to create variants with enhanced phosphatase activity. Specific amino acid substitutions (e.g., D132N, E133Q) were introduced to optimize the protein's catalytic parameters, resulting in improved retinol production stability while maintaining high productivity through microbial fermentation

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If microbial fermentation is used for retinol production, then production cost is reduced, but production stability deteriorates

Engineering Contradiction:

Improveproduction costVSAvoidproduction stability

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent improves production stability in microbial fermentation by engineering PHO84 protein variants with optimized catalytic parameters. The mutated PHO84 proteins exhibit enhanced phosphatase activity and stability under fermentation conditions, ensuring consistent retinol production while maintaining the cost advantages of microbial fermentation over chemical synthesis

Inventive Principle:

Principle #35Parameter changes

3Productivity

If endogenous PHO84 activity is used, then genetic complexity is minimized, but retinoid production increases insufficiently

Engineering Contradiction:

Improveretinoid productionVSAvoidgenetic modification complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent achieves significant retinoid production enhancement through targeted parameter changes in the PHO84 protein sequence. By introducing specific point mutations (single or combined) in the PHO84 coding sequence, the invention optimizes protein activity parameters without requiring complex multi-gene modifications, thus achieving high productivity with relatively simple genetic engineering approaches

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4671375A1Yarrowia sp. microorganism for producing retinoid with increased PHO84 protein activity and retinoid production method using same

Publication Date: 2025.12.31 CJ CHEILJEDANG CORP

Figure 1

AI summary

The present application relates to: a Yarrowia sp. microorganism with retinoid production ability, in which the activity of the PHO84 protein is increased compared to the endogenous activity thereof; a retinoid production method using same; a method for producing a Yarrowia sp. microorganism with retinoid production ability; and a composition for producing a retinoid.