Valencene Synthase Polypeptides for Terpene Production

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Solution Overview

Problem

Current methods for producing valencene and nootkatone in large quantities are economically unviable due to the complex structures of these compounds, and existing synthetic processes are inefficient.

Innovation Solution

Development of recombinant cells expressing valencene synthase polypeptides with at least 85% sequence identity to a specific valencene synthase, which catalyze the production of valencene and aristolochene from acyclic pyrophosphate terpene precursors, such as farnesyl diphosphate, using nucleic acid molecules encoding these synthases and suitable host cells like yeast.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If chemical approaches are used to generate valencene and nootkatone, then the compounds can be produced, but the highly complex structures make economically viable synthetic processes unattainable

Engineering Contradiction:
Improveeconomic viability of synthesisVSAvoidstructural complexity of compounds
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent replaces complex chemical synthesis mechanisms with biological enzymatic mechanisms. Valencene synthase enzymes catalyze the cyclization of farnesyl diphosphate to produce valencene, substituting multi-step chemical synthesis with a single enzymatic reaction that occurs under mild physiological conditions, thereby achieving economic viability despite structural complexity

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

Solution Approach 2:

The patent introduces enzymatic intermediaries (valencene synthase proteins and their coding nucleic acids) to mediate the production of complex terpenes. These biological intermediaries simplify the manufacturing process by providing catalytic pathways that are more efficient and economically viable than direct chemical synthesis approaches

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If valencene is extracted from Valencia orange peel, then natural valencene is obtained, but the production quantity is limited and economically inefficient

Engineering Contradiction:
Improveproduction quantity of valenceneVSAvoideconomic efficiency of extraction
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent creates recombinant copies of valencene synthase genes from Eryngium glaciale and expresses them in host cells such as yeast. This copying and expression system enables规模化 production of valencene through fermentation, dramatically increasing production quantity beyond what is possible through natural extraction while reducing economic costs

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent employs host cells that are engineered to self-produce valencene through the expressed valencene synthase enzyme. The system uses the host cell's own metabolic machinery to convert farnesyl diphosphate into valencene, eliminating the need for external extraction processes and enabling sustainable, high-volume production

Inventive Principle:
Principle #25Self-service

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 the production of valencene and other terpenes in high quantities, including the conversion of valencene to nootkatone, offering a cost-effective and energy-efficient method for producing valuable terpene products.

Implementation Method 1

valencene synthase polypeptide having at least 85% sequence identity to the sequence set forth in SEQ ID NO: 1, or a catalytically active fragment thereof

Methodology Applied
Scientific EffectCatalysis: Catalysis

Data Source

PatentEP3085778B1Valencene synthase polypeptides, encoding nucleic acid molecules and uses thereof
Publication Date: 2021.07.07 EVOLVA INC
  • EP3085778B1 patent drawingFigure 1
  • EP3085778B1 patent drawingFigure 2A
  • EP3085778B1 patent drawingFigure 2B

AI summary

The present invention is directed to a recombinant cell that produces valencene and aristolochene, wherein the recombinant cell comprises a heterologous nucleic acid that encodes a valencene synthase polypeptide, or a catalytically active fragment thereof; or the recombinant cell comprises a heterologous valencene synthase polypeptide, or a catalytically active fragment thereof. The presnt invention also provides methods of producing valencene and aristolochene using a recombinant cell of the invention and compositions comprising valencene and aristolochene.