Recombinant Host Cells Expressing MAE1 Transport Proteins

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Solution Overview

Problem

Current petrochemical-based production routes for malonate and malonate-derived compounds are low-yielding, environmentally damaging, and dependent on non-renewable feedstocks, with a need for improved biocatalytic conversion of renewable feedstocks into malonate and subsequent purification and preparation of downstream chemicals.

Innovation Solution

Genetic modifications in recombinant host cells, specifically using nucleic acids encoding MAE1 transport proteins, enhance malonate production, with suitable MAE1 transport proteins obtained from eukaryotic organisms like Aspergillus species, to increase titer and yield, and recombinant expression vectors are used to express these proteins in host cells such as Pichia kudriavzevii for efficient malonate production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If petrochemical-based production routes are used for malonate, then production capacity is maintained, but environmental damage increases and dependency on non-renewable feedstocks worsens

Engineering Contradiction:
Improvemalonate production capacityVSAvoidenvironmental damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces petrochemical-based mechanical/chemical production systems with a biological system using recombinant host cells. The host cells are genetically modified to express transport proteins that enable them to produce malonate from renewable feedstocks, substituting the traditional petrochemical process with a biologically-based system that reduces environmental harm while maintaining productivity

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

Solution Approach 2:

The patent changes the fundamental parameters of the production system by switching from non-renewable petroleum feedstocks to renewable carbon sources. The genetic modification of host cells alters their metabolic parameters to enable malonate production, transforming the production pathway from a harmful chemical process to a sustainable biological process

Inventive Principle:
Principle #35Parameter changes

2Productivity

If petrochemical-based production routes are used for malonate, then production experience is available, but low yield and high cost persist

Engineering Contradiction:
Improvemalonate yieldVSAvoidproduction cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The recombinant host cells are engineered to self-produce malonate through their own metabolic processes. The transport proteins expressed in the host cells enable the cells to autonomously convert renewable feedstocks into malonate, eliminating the need for complex external chemical processing steps and reducing production costs while improving yield

Inventive Principle:
Principle #25Self-service

3Object-affected harmful factors

If existing biocatalytic conversion methods are used, then renewable feedstocks are utilized, but malonate production efficiency is insufficient

Engineering Contradiction:
Improveenvironmental impact reductionVSAvoidmalonate production efficiency
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent introduces transport proteins that create a feedback mechanism within the host cell system. These proteins regulate the transport of substrates and products, optimizing the metabolic flux toward malonate production. This feedback control enhances production efficiency while maintaining the environmental benefits of using renewable feedstocks

Inventive Principle:
Principle #23Feedback

Data Source

PatentUS10385368B2Recombinant host cells for the production of malonate
Publication Date: 2019.08.20 LYGOS INC

AI summary

Compositions and methods for producing malonate in recombinant host cells in order to increase malonate titer, yield, and/or productivity are provided. Recombinant host cells comprising nucleic acids encoding MAE1 transport proteins that increase production of malonate by the host cell and vectors for expressing MAE1 transport proteins that increase production of malonate by the host cell are also disclosed.