Engineered Cells With Membrane Transporters for Melatonin Production

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Solution Overview

Problem

Current methods for producing melatonin and 5HTP are costly and inefficient, relying heavily on chemical synthesis or plant extraction, with a need for biologically engineered cells that can effectively transport and produce these compounds.

Innovation Solution

Genetically modified recombinant cells overexpressing integral membrane proteins such as YhjV, GarP, ArgO, AcrAB, and LysP to enhance the export and import of indole-derivatives like melatonin and 5HTP, utilizing biosynthetic pathways involving enzymes like L-tryptophan hydroxylase and 5HTP decarboxylase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical synthesis or plant extraction is used for producing melatonin and 5HTP, then production can be achieved, but the process is costly and inefficient

Engineering Contradiction:
Improveproduction efficiencyVSAvoidproduction cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent replaces chemical synthesis methods with biological production systems using recombinant cells. The cells are engineered to express biosynthetic pathways for melatonin and 5HTP production, substituting chemical processes with enzymatic reactions catalyzed by expressed proteins, thereby reducing production costs and improving efficiency

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

Solution Approach 2:

The recombinant cells are designed to autonomously produce melatonin and 5HTP through engineered biosynthetic pathways. The cells utilize their own metabolic machinery and imported substrates to synthesize the compounds, eliminating the need for external chemical synthesis processes and reducing overall production costs

Inventive Principle:
Principle #25Self-service

2Productivity

If recombinant cells are engineered to produce melatonin and 5HTP, then natural production is achieved, but transporters must be engineered to improve export and reduce toxicity

Engineering Contradiction:
Improveproduct titerVSAvoidcellular toxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes toxic indole-derivatives from the cellular interior through engineered transporter proteins. These transporters actively pump melatonin, 5HTP, and other indole compounds from the cytoplasm across the cell membrane into the extracellular environment, thereby reducing intracellular toxicity while maintaining production levels

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The transporter proteins serve as intermediary molecules that facilitate the controlled movement of indole-derivatives between the cell interior and exterior. These membrane proteins mediate the export process, allowing the cell to maintain high production levels while managing toxicity through regulated transport

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If transporters are overexpressed to improve export of indole-derivatives, then production and tolerance increase, but device complexity increases

Engineering Contradiction:
Improveproduction yieldVSAvoidgenetic modification complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into the transporter protein expression system. The same overexpressed transporter proteins simultaneously achieve multiple objectives: exporting toxic compounds, maintaining cellular homeostasis, and enabling scalable production. This consolidation reduces the need for separate genetic modifications for each function

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The engineered transporter proteins perform multiple functions within the recombinant cell system. They serve as export mechanisms for various indole-derivatives, contribute to cellular tolerance, and enable product recovery. This multi-functionality reduces the overall complexity compared to having separate systems for each purpose

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 overexpression of these transporters increases production and tolerance to indole-derivatives, improving fermentation yields and reducing toxicity, thereby enhancing the efficiency and cost-effectiveness of melatonin and 5HTP production.

Implementation Method 1

Transporters are responsible for cellular exchange of both small molecules and macromolecules

Methodology Applied
Scientific EffectTransport: Permeation

Implementation Method 2

L-tryptophan hydroxylase; (b) an L-tryptophan hydroxylase and a 5HTP decarboxylase

Methodology Applied
Scientific EffectEnzymatic reaction: Enzyme

Data Source

PatentUS12359176B2Engineered cells for production of indole-derivatives
Publication Date: 2025.07.15 DANMARKS TEKNISKE UNIV
  • US12359176B2 patent drawing
  • US12359176B2 patent drawing
  • US12359176B2 patent drawing

AI summary

Integral membrane proteins capable of transporting melatonin and other indole-derivatives across biological membranes, and uses thereof.