Mogroside Biosynthesis via Engineered Host Cells

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Solution Overview

Problem

The production of mogrosides, used as natural sweeteners, is hindered by labor-intensive extraction from natural sources and high costs associated with de novo synthesis, due to limited characterization of enzymes involved in biosynthesis and structural complexity.

Innovation Solution

Engineered host cells expressing heterologous polynucleotides encoding UDP-glycosyltransferase (UGT) enzymes, along with other enzymes like cucurbitadienol synthase, C11 hydroxylase, cytochrome P450 reductase, epoxide hydrolase, and squalene epoxidase, to efficiently produce mogrol and mogrosides, overcoming the limitations of natural biosynthesis and extraction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mogrosides are extracted from natural fruit sources, then natural sweeteners are obtained, but the extraction process becomes labor-intensive and costly

Engineering Contradiction:

Improvenatural source authenticityVSAvoidextraction efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent utilizes the host cell's own metabolic machinery and engineered enzymatic pathways to produce mogrosides internally, eliminating the need for external extraction processes. The recombinant cells self-generate the target compounds through heterologous gene expression and enzymatic catalysis of biosynthetic pathways.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent replaces mechanical extraction methods with biological synthesis. Instead of using physical or chemical extraction processes to obtain mogrosides from fruit, the invention employs genetically engineered cells that biosynthesize mogrosides through enzymatic reactions, substituting mechanical extraction with biological production.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If de novo chemical synthesis is used to produce mogrosides, then production can be controlled, but the structural complexity leads to high costs

Engineering Contradiction:

Improveproduction controlVSAvoidsynthesis pathway complexity

Core Design Contradiction:

Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent replaces complex chemical synthesis with biological synthesis. Instead of using multi-step chemical reactions to build the complex mogroside structure, the invention employs enzymatic catalysis in recombinant cells, where enzymes naturally perform the complex transformations with high specificity and efficiency.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the fundamental parameter of synthesis from chemical to biological. By switching from chemical reagents and conditions to enzymatic catalysis in living cells, the process achieves better control over stereochemistry and reduces the number of steps required to produce the complex structure.

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If limited enzyme characterization is used, then research scope is maintained, but biosynthesis efficiency remains limited

Engineering Contradiction:

Improveresearch flexibilityVSAvoidbiosynthesis efficiency

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent segments the mogroside biosynthesis pathway into discrete enzymatic steps, each catalyzed by a specific enzyme. By identifying and characterizing individual enzymes (such as UGTs, P450s, and other pathway enzymes) separately, the invention enables targeted optimization of each step while maintaining overall pathway functionality and flexibility.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces intermediary compounds and enzymes to bridge gaps in the biosynthetic pathway. By characterizing and expressing specific intermediate metabolites and the enzymes that produce them, the invention enables stepwise optimization of the pathway while maintaining flexibility in engineering different mogroside variants.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 enables cost-effective and efficient production of mogrosides, reducing production costs and improving yield by utilizing genetically engineered cells to catalyze specific conversions in mogrol biosynthesis pathways.

Implementation Method 1

host cells that comprise a heterologous polynucleotide encoding a UDP-glycosyltransferase (UGT), wherein the UGT is capable of catalyzing conversion of mogrol to MIA1

Methodology Applied