Phosphatidylserine Production via Enzyme Inactivation

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Solution Overview

Problem

There is a lack of an economically viable and stable method for producing phosphatidylserine with a high content of polyunsaturated fatty acids, particularly DHA-bonded phosphatidylserine, from a safe starting material, due to issues with phospholipase A2 residue and hydrolysis during synthesis processes.

Innovation Solution

A method involving esterification of polyunsaturated fatty acids with lysophospholipid using phospholipase A2, followed by adjusting enzyme activity to 10 U/g or less, and performing a base exchange reaction with serine in the presence of phospholipase D to form phosphatidylserine, while removing or inactivating phospholipase A2 to prevent detachment of the fatty acid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If phospholipase A2 is used to hydrolyze fatty acid at 2-position of phospholipid, then lysophospholipid is obtained, but phospholipase A2 remains in the product causing DHA detachment during storage

Engineering Contradiction:
Improveproduction of lysophospholipidVSAvoidstability of DHA bonding
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent applies preliminary action by inactivating phospholipase A2 through specific treatment (heating at 60-80°C for 30 minutes or adding calcium ions) before the DHA bonding step. This preliminary inactivation prevents the enzyme from causing DHA detachment during subsequent storage and processing, thereby ensuring product stability while maintaining ease of manufacture.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If phospholipase D is used for serylation of phospholipid, then phosphatidylserine is formed, but hydrolysis at 2-position occurs requiring water

Engineering Contradiction:
Improvesynthesis of phosphatidylserineVSAvoidhydrolysis at 2-position
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by pre-inactivating phospholipase A2 and controlling reaction conditions (pH 7.5-8.5, temperature 37-42°C) before initiating the phospholipase D-mediated serylation. This prevents hydrolysis at the 2-position from occurring as a harmful side reaction, allowing efficient phosphatidylserine synthesis without compromising product integrity.

Inventive Principle:
Principle #9Preliminary anti-action

3Reliability

If DHA-bonded phosphatidylcholine is extracted from fish tissues, then DHA-bonded phosphatidylserine can be synthesized, but starting material is expensive and supply is unstable

Engineering Contradiction:
Improvesupply stability of starting materialVSAvoidcost of production
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces expensive, supply-unstable fish tissue-derived phospholipids with cheaper, readily available plant-derived phospholipids (soybean lecithin, sunflower lecithin, or rapeseed lecithin). Although plant phospholipids have different fatty acid profiles, the process achieves the desired DHA-bonded phosphatidylserine product through enzymatic modification, dramatically reducing production costs and ensuring stable supply while maintaining product quality.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 method allows for the stable and cost-effective production of phospholipid compositions with 10% or more phosphatidylserine and 10-40% polyunsaturated fatty acids, ensuring effective bonding and stability of DHA-bonded phosphatidylserine.

Implementation Method 1

performing an esterification reaction of a polyunsaturated fatty acid with lysophospholipid using phospholipase A2 to obtain phospholipid

Methodology Applied
Scientific EffectEsterification reaction: Chemical Bonding

Implementation Method 2

using phospholipase A2 (PLA2) to obtain phospholipid

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

performing a base exchange reaction of a mixture including the phospholipid and serine in the presence of phospholipase D (PLD) to form a phospholipid-containing composition which includes phosphatidylserine

Methodology Applied
Scientific EffectBase exchange reaction: Chemical Bonding

Data Source

PatentUS10160984B2Method for producing phospholipid-containing composition, and phospholipid-containing composition
Publication Date: 2018.12.25 KANEKA CORP

AI summary

A method for producing a phospholipid-containing composition which includes 10% by weight or more of phosphatidylserine based on the whole phospholipid-containing composition, a content of a polyunsaturated fatty acid being from 10 to 40% by weight based on the total amount of constituent fatty acids, the method including the following steps (1) and (2) in this order, and the following steps (3) and (4) in this order inexpensively and stably supplies a phospholipid-containing composition which includes phosphatidylserine to which a large amount of the polyunsaturated fatty acid is bonded at the 2-position thereof. Step (1): performing an esterification reaction of a polyunsaturated fatty acid with lysophospholipid using phospholipase A2 (PLA2) to obtain phospholipid. Step (2): adjusting an activity of PLA2 in the phospholipid to 10 U/g (phospholipid) or less after the step (1). Step (3): performing a base exchange reaction of a mixture including the phospholipid and serine in the presence of phospholipase D (PLD) to form a phospholipid-containing composition which includes phosphatidylserine. Step (4): separating the composition.