Yeast Metabolic Engineering for Phytosphingosine Yield

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Solution Overview

Problem

Current methods for producing phytosphingosine (PHS) and sphinganine (DHS) using yeast are inefficient, as they rely on unoptimized genetic regulation of key enzymes, limiting production yields.

Innovation Solution

Modifying yeast to reduce the expression and activity of LCB4 and CKA2 genes, while increasing the expression of LCB1, LCB2, TSC10, and SUR2 genes, and using additives like cyclodextrin to enhance production, results in improved yields of PHS and DHS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If unoptimized genetic regulation is used in yeast for producing PHS and DHS, then the production process is simple, but the production yield is low

Engineering Contradiction:
Improveproduction yield of PHS and DHSVSAvoidgenetic modification complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by modifying the expression levels of specific genes (LCB4, CKA2, LCB1, LCB2, TSC10, SUR2) to optimize the biosynthetic pathway. By reducing LCB4 and CKA2 expression while increasing LCB1, LCB2, TSC10, and SUR2 expression, the patent achieves higher production yields of PHS and DHS through controlled genetic parameter adjustment.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent segments the genetic regulation into distinct functional modules: downregulating genes (LCB4, CKA2) that limit production and upregulating genes (LCB1, LCB2, TSC10, SUR2) that enhance the biosynthetic pathway. This segmentation allows independent optimization of each genetic element's contribution to overall production efficiency.

Inventive Principle:
Principle #1Segmentation

2Productivity

If multiple gene expressions are modified to enhance production, then the production yield increases, but the manufacturing process becomes more complex

Engineering Contradiction:
Improveproduction yield of PHS and DHSVSAvoidease of genetic modification
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent systematically changes expression parameters of six key genes to optimize production. By coordinating the downregulation of LCB4 and CKA2 with the upregulation of LCB1, LCB2, TSC10, and SUR2, the patent creates a synergistic effect that enhances production yield while maintaining a manageable level of genetic modification complexity through focused target selection.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11111511B2Method for producing phytosphingosine or sphinganine
Publication Date: 2021.09.07 AJINOMOTO CO INC
  • US11111511B2 patent drawing
  • US11111511B2 patent drawing

AI summary

A method for producing an objective substance such as phytosphingosine and sphinganine using yeast is provided. An objective substance is produced by cultivating yeast having an ability to produce the objective substance and modified so that the expression and/or activities of proteins encoded by LCB4 and CKA2 genes are reduced in a culture medium, and collecting the objective substance from cells of the yeast and/or the culture medium.