Enzymatic Retinyl Ester Production via Acyltransferase

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Solution Overview

Problem

Current chemical production methods for retinoids, including vitamin A, are inefficient due to high energy consumption, complex purification steps, and the production of undesirable by-products, while biological systems produce retinoids at low levels and with instability, making commercial-scale isolation impractical.

Innovation Solution

A novel enzymatic process using acyltransferase enzymes to convert retinol into retinyl esters, particularly long chain retinyl esters, in a carotenoid-producing host cell, such as a fungal host cell, which enhances productivity and specificity by expressing heterologous acyltransferases like DGATs and ARATs, optimizing the conversion rate to at least 20% long chain retinyl esters.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical production methods are used for retinoids, then production capacity is sufficient, but energy consumption is high and purification steps are complicated

Engineering Contradiction:
Improveproduction capacityVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by stationary object

Solution Approach 1:

The patent replaces chemical production methods with a biological system (microorganism-based enzymatic conversion) to produce retinyl esters. This substitution eliminates the need for high-energy chemical reactions and complex purification steps while maintaining production capacity, directly resolving the contradiction between productivity and energy consumption.

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

2Productivity

If chemical production methods are used for retinoids, then production capacity is sufficient, but purification steps are complicated

Engineering Contradiction:
Improveproduction capacityVSAvoidpurification steps
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces chemical production methods with a biological system that naturally produces retinyl esters with high specificity. The microorganism-based system converts beta-carotene to retinol and then to retinyl esters through endogenous enzymes, eliminating the need for complex chemical purification steps while maintaining production capacity.

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

3Use of energy by stationary object

If biological systems are used for retinoid production, then energy consumption is reduced, but production levels are low and instability occurs

Engineering Contradiction:
Improveenergy consumptionVSAvoidproduction levels
Core Design Contradiction:
Use of energy by stationary objectVSProductivity

Solution Approach 1:

The patent optimizes multiple parameters of the biological system including: selecting specific microorganism strains with high retinoid production capability, optimizing culture conditions (temperature, pH, nutrients), enhancing enzyme activity through genetic modification, and controlling the conversion pathway from beta-carotene to retinyl esters. These parameter changes collectively increase production levels while maintaining low energy consumption and high stability.

Inventive Principle:
Principle #35Parameter changes

4Use of energy by stationary object

If biological systems are used for retinoid production, then energy consumption is reduced, but product specificity is low and by-products are high

Engineering Contradiction:
Improveenergy consumptionVSAvoidproduct specificity
Core Design Contradiction:
Use of energy by stationary objectVSManufacturing precision

Solution Approach 1:

The patent enhances product specificity by optimizing the enzymatic conversion pathway parameters. Specific enzymes are selected and optimized to catalyze the conversion of retinol to retinyl esters with high specificity, minimizing by-product formation. The culture conditions and substrate composition are adjusted to favor the desired reaction pathway, achieving high manufacturing precision while maintaining low energy consumption.

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

This process improves the productivity and specificity of retinyl ester production, reducing by-product formation and energy consumption, enabling more economical and ecological production of vitamin A and its precursors, with a high percentage of trans-isoforms, thus addressing the limitations of existing methods.

Implementation Method 1

a novel enzymatic process using acyltransferase enzymes to convert retinol into retinyl esters

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 2

conversion of retinol into retinyl long chain esters via conversion of retinol

Methodology Applied
Scientific EffectAcylation: Chemical Bonding

Data Source

PatentUS11905542B2Production of retinyl esters
Publication Date: 2024.02.20 DSM IP ASSETS BV

AI summary

The present invention is related to a novel enzymatic process for production of retinyl esters, such as in particular retinyl long chain esters, via conversion of retinol, which process includes the use of enzymes having acyltransferase activity. Said process might be used for biotechnological production of vitamin A.