Modified Santalene Synthase Enzymes for Sustainable Sandalwood Oil Production

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Solution Overview

Problem

The perfume industry faces challenges in obtaining sandalwood oil efficiently and cost-effectively due to the complex structures of santalols and other sesquiterpenoids, which have hindered the development of economically viable synthetic processes, and natural sandalwood resources are depleted.

Innovation Solution

Modified santalene synthase polypeptides and nucleic acid molecules that encode these enzymes are provided, which catalyze the production of santalenes and santalols from farnesyl diphosphate, allowing for increased terpene production and altered product profiles in host cells such as yeast.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If sandalwood oil is obtained by distillation of heartwood from natural Santalum species, then the sandalwood fragrance components (santalols and sesquiterpenoids) are obtained, but natural sandalwood resources are depleted due to centuries of over-exploitation

Engineering Contradiction:

Improvesandalwood oilVSAvoidnatural resource depletion

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent creates a biological copy of the sandalwood oil production system by introducing santalene synthase genes into yeast cells. The yeast cells then produce santalenes and santalols that replicate the chemical composition of natural sandalwood oil, providing a renewable alternative to depleted natural resources.

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent uses modified santalene synthase enzymes as intermediaries to convert farnesyl diphosphate into santalenes and santalols. These engineered enzymes act as biological catalysts that mediate the production of sandalwood fragrance components in a controlled, sustainable manner without requiring natural sandalwood trees.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If chemical approaches are used to generate santalols and sesquiterpenoids, then sandalwood fragrance components can be produced, but the highly complex structures of these compounds have rendered economically viable synthetic processes unattainable

Engineering Contradiction:

Improvesantalols and sesquiterpenoidsVSAvoidsynthetic process

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent replaces complex chemical synthesis mechanisms with biological enzymatic mechanisms. Instead of using multi-step chemical reactions to build the complex santalol and sesquiterpenoid structures, the invention uses santalene synthase enzymes to catalyze the formation of these compounds through natural biosynthetic pathways, dramatically simplifying the manufacturing process.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent modifies the santalene synthase enzyme through site-directed mutagenesis to optimize its catalytic activity and product profile. By changing specific amino acid residues in the enzyme sequence, the invention enhances the production of desired santalols and sesquiterpenoids, making the biological synthesis process economically viable.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If modified santalene synthase polypeptides are used to increase terpene production, then production efficiency is improved, but the enzyme structure and function must be precisely modified to achieve desired product profiles

Engineering Contradiction:

Improveterpene productionVSAvoidenzyme modification

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies local quality modification by making specific, targeted changes to particular amino acid residues within the santalene synthase enzyme structure. Rather than attempting to redesign the entire enzyme, the invention focuses on modifying specific local regions (such as residues 183, 206, and 282) that directly influence catalytic activity and product distribution, achieving high productivity with controlled modifications.

Inventive Principle:

Principle #3Local quality

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

These modified synthases enhance the production of terpene products like santalenes and santalols, offering a more efficient and cost-effective method for producing sandalwood fragrance components, overcoming the limitations of natural resource depletion and chemical synthesis complexities.

Implementation Method 1

santalene synthases are terpene synthases that catalyze the formation of santalenes and bergamotene, including α-santalene, β-santalene, α-exo-bergamotene and epi-β-santalene, from the acyclic pyrophosphate terpene precursor farnesyl diphosphate (FPP)

Methodology Applied

Scientific EffectCatalysis: Catalysis

Data Source

PatentUS9714418B2Modified santalene synthase polypeptides, encoding nucleic acid molecules and uses thereof

Publication Date: 2017.07.25 LALLEMAND BIO INGREDIENTS USA LLC

AI summary

Provided are modified santalene synthase polypeptides, nucleic acid molecules encoding the modified santalene synthase polypeptides, and methods of using the modified santalene synthase polypeptides. The modified santalene synthase polypeptides include those that catalyze production of increased levels of terpenes or altered profiles thereof or both.