Valencene Synthase Mutations for Industrial Production

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Solution Overview

Problem

Current valencene synthases have drawbacks such as impaired production rates, low specificity, and significant side product formation, particularly at neutral or alkaline pH, making them unsuitable for industrial valencene production.

Innovation Solution

A novel valencene synthase with a specific amino acid sequence or its functional homologue, which displays improved expression and specificity towards valencene synthesis, reducing side product formation and increasing production rates in host cells like E. coli and Saccharomyces cerevisiae.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If known valencene synthases from citrus are used for industrial production, then valencene can be produced, but the production rate is impaired and side product formation is significant

Engineering Contradiction:
Improvevalencene production rateVSAvoidspecificity of valencene synthesis
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent changes the amino acid sequence parameters of the valencene synthase enzyme by introducing specific mutations (e.g., substituting hydrophobic residues with polar or charged residues in the substrate binding pocket). These parameter changes in the enzyme's molecular structure improve its catalytic efficiency and substrate specificity, thereby increasing valencene production rate while reducing side product formation compared to wild-type citrus valencene synthases

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a modified copy of the valencene synthase gene from non-citrus sources (such as conifers) and optimizes it for industrial production. This copied and adapted enzyme retains the core catalytic function but exhibits improved productivity and specificity when expressed in host organisms like E. coli or Saccharomyces cerevisiae, solving the limitations of direct citrus enzyme use

Inventive Principle:
Principle #26Copying

2Productivity

If valencene synthase is expressed in host cells for in vivo production, then continuous valencene synthesis is possible, but expression levels are low and production rates are impaired

Engineering Contradiction:
Improvevalencene production rateVSAvoidexpression level of valencene synthase
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs host cells (E. coli, Saccharomyces cerevisiae) that possess endogenous farnesyl diphosphate (FPP) biosynthesis pathways. The introduced valencene synthase enzyme utilizes these naturally available FPP substrates without requiring external supplementation, enabling self-sufficient continuous valencene production. The host cell's metabolic machinery serves the foreign enzyme, improving expression reliability and productivity

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent separates the valencene synthase gene from its native citrus genomic context and places it under the control of strong, constitutive promoters in expression vectors. This segmentation allows independent optimization of expression levels using host-specific regulatory elements, significantly improving transcription efficiency and protein expression levels compared to native promoter-driven expression

Inventive Principle:
Principle #1Segmentation

3Quantity of substance

If distillation from citrus essential oils is used to obtain valencene, then valencene can be isolated, but the process is cumbersome due to low valencene concentration

Engineering Contradiction:
Improvevalencene concentrationVSAvoidsimplicity of isolation process
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent replaces the mechanical distillation process with a biological production system. Instead of physically separating valencene from citrus essential oils through complex distillation equipment, the invention uses genetically engineered microorganisms to directly synthesize and secrete valencene into the culture medium, where it can be extracted through simpler methods, thereby improving ease of manufacture while increasing effective valencene concentration

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

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

The novel valencene synthase achieves higher valencene production rates and improved specificity compared to existing synthases, with a molar ratio of valencene to germacrene A of 4:1, and demonstrates enhanced activity at neutral or alkaline pH, suitable for industrial applications.

Implementation Method 1

farnesyl diphosphate (FPP) is enzymatically converted into valencene in the presence of a valencene synthase

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS9260709B2Valencene synthase from callitropsis nootkatensis
Publication Date: 2016.02.16 BASF NEDERLAND BV

AI summary

The present invention relates to a valencene synthase, to a nucleic acid encoding such valencene synthase, to a host cell comprising said encoding nucleic acid sequence and to a method for preparing valencene, comprising converting farnesyl diphosphate to valencene in the presence of a valencene synthase according to the invention.