BAHD Alcohol Acyltransferases for Stable Cannabinoid Acylation

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Solution Overview

Problem

There is a need for methodologies to acylate cannabinoids to enhance their stability and processability, as existing acyltransferases have not been identified for this purpose, limiting their development as therapeutic agents.

Innovation Solution

Identification of novel BAHD alcohol acyltransferases (AATs) that catalyze the acylation of cannabinoids, specifically from Helichrysum umbraculigerum, enabling the production of acylated forms of CBGA-type cannabinoids and geranylated O-acylated amorfrutins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If acylation of cannabinoids is performed to enhance stability, then thermal stability is improved, but the enzyme catalysis capability is insufficient because no acyltransferases have been identified for this purpose

Engineering Contradiction:
Improvethermal stability of cannabinoidsVSAvoidenzyme availability for acylation
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent introduces BAHD alcohol acyltransferases as intermediary enzymes that mediate the acylation reaction between cannabinoids and acyl donors. These enzymes serve as the missing link that enables stable acylation of cannabinoids, resolving the contradiction between improving thermal stability through acylation and the lack of available enzymes to perform this modification.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If large-scale acylation of cannabinoids is achieved, then productivity is improved, but device complexity increases due to the need for transgenic systems

Engineering Contradiction:
Improvelarge-scale acylation capacityVSAvoidtransgenic cell system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs transgenic cells that autonomously express the BAHD alcohol acyltransferase enzyme and perform acylation of cannabinoids within the cell system. The transgenic cells serve themselves by incorporating the enzyme gene and automatically carrying out the acylation reaction when provided with substrates, eliminating the need for external enzyme addition and simplifying large-scale 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

The identified AATs facilitate the large-scale acylation of cannabinoids, potentially increasing their stability and applicability as therapeutic agents without hindering their pharmacological activities.

Implementation Method 1

two novel BAHD alcohol acyltransferases (AATs) that catalyze the acylation of the naturally occurring and some additional unique cannabinoids

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS20250327043A1Alcohol acyltransferase and a transgenic cell, tissue, and organism comprising same
Publication Date: 2025.10.23 YEDA RES & DEV CO LTD
  • US20250327043A1 patent drawing
  • US20250327043A1 patent drawing
  • US20250327043A1 patent drawing

AI summary

The present invention provides polynucleotide sequences derived from Helichrysum umbraculigerum and encoding a protein or a plurality thereof belonging to the alcohol acyltransferase (AAT) family. Further provided are an artificial nucleic acid molecule including the polynucleotide disclosed herein, a transgenic cell, tissue, or plant including same.