SHC Enzyme Variants for Homofarnesol-to-Ambrox Cyclization

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Solution Overview

Problem

Existing methods for producing (−)-Ambrox and Ambra oxide are inefficient and lack improved methods for cyclizing other substrates to form compounds useful in fragrances.

Innovation Solution

Development of SHC/HAC enzyme variants with specific amino acid alterations, such as M132R, A224V, and I432T, to enhance the enzymatic conversion of (3E,7E)-homofarnesol to (−)-Ambrox and E,E-bishomofarnesol to Ambra oxide, improving conversion rates and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If wild-type SHC enzymes are used for converting homofarnesol to Ambrox, then the basic cyclization function is achieved, but the conversion rate and selectivity are insufficient

Engineering Contradiction:

Improveconversion rateVSAvoidselectivity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying specific amino acid residues in the SHC enzyme sequence (positions 132, 224, 432, 557, and other positions). These sequence variations create enzyme variants with altered catalytic properties, achieving both improved conversion rates and enhanced selectivity for Ambrox production from homofarnesol substrates

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If existing SHC enzymes are used, then cyclization of squalene to hopene occurs, but efficient production of Ambrox and Ambra oxide with high selectivity is not achieved

Engineering Contradiction:

ImproveselectivityVSAvoidproduction efficiency

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent modifies enzyme sequence parameters at specific positions (132, 224, 432, 557, and others) to create variants that simultaneously achieve high selectivity for desired products (Ambrox, Ambra oxide) and high productivity. The sequence variations optimize the enzyme's catalytic efficiency and substrate specificity

Inventive Principle:

Principle #35Parameter changes

3Productivity

If wild-type SHC enzyme is used, then the enzymatic conversion function is provided, but the conversion efficiency and product selectivity remain suboptimal

Engineering Contradiction:

Improveconversion efficiencyVSAvoidproduct selectivity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent employs parameter changes by introducing specific amino acid substitutions at key positions in the SHC enzyme sequence. These changes optimize the enzyme's active site configuration and catalytic mechanism, resulting in variants that achieve both superior conversion efficiency and product selectivity for Ambrox and Ambra oxide synthesis

Inventive Principle:

Principle #35Parameter changes

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 SHC/HAC enzyme variants demonstrate enhanced conversion rates and selectivity, enabling efficient production of (−)-Ambrox and Ambra oxide for use in fragrances and cosmetics.

Implementation Method 1

enzymatically converting (3E,7E)-homofarnesol (EEH) or a mixture of isomers of homofarnesol comprising EEH to (−)-Ambrox

Methodology Applied

Scientific EffectEnzymatic conversion: Enzyme

Implementation Method 2

enzymatically converting E,E-bishomofarnesol to Ambra oxide

Methodology Applied

Scientific EffectEnzymatic conversion: Enzyme

Data Source

PatentUS12416027B2Squalene hopene cyclase (SHC) variants

Publication Date: 2025.09.16 GIVAUDAN SA

AI summary

Squalene Hopene Cyclase (SHC) enzymes and variants thereof and their uses for making (−)-Ambrox from homofarnesol and Ambra oxide from bishomofarnesol.