Engineered Microbial Pathways for Renewable Terephthalate Production

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Solution Overview

Problem

Current methods for producing terephthalate (PTA) are costly and rely on petrochemical sources, with limited biosynthetic pathways available for renewable production due to the irreversible nature of monooxygenases involved in bacterial degradation.

Innovation Solution

Design and production of non-naturally occurring microbial organisms with engineered metabolic pathways to biosynthesize p-toluate and terephthalate from carbohydrate feedstocks, utilizing enzymes like 2-dehydro-3-deoxyphosphoheptonate synthase and shikimate pathway enzymes to convert (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate to p-toluate and subsequently to terephthalate.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monooxygenases are used for bacterial degradation of aromatic compounds, then degradation capability is achieved, but biosynthetic capability is lost due to irreversible reaction direction

Engineering Contradiction:
Improvedegradation capabilityVSAvoidbiosynthetic capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies reverse engineering to the monooxygenase pathway by introducing enzymes that catalyze reactions in the opposite direction of natural degradation. Specifically, it uses p-toluate synthase to convert shikimic acid derivatives to p-toluate, and terephthalate synthase to convert p-toluate to terephthalate, thereby inverting the natural degradative pathway into a biosynthetic route.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent introduces p-toluate as an intermediate compound that bridges the shikimate pathway and terephthalate production. The engineered pathway uses shikimic acid as a starting material, converts it to p-toluate through p-toluate synthase, and then to terephthalate through terephthalate synthase, creating a multi-step intermediary pathway that enables renewable production.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If petrochemical oxidation processes are used for PTA production, then production scale is achieved, but cost-effectiveness and renewability are reduced

Engineering Contradiction:
Improveproduction scaleVSAvoidcost-effectiveness
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent employs engineered microorganisms that autonomously perform the biosynthesis of terephthalate from renewable carbohydrate feedstocks through their metabolic pathways. The microorganisms self-convert sugars to shikimic acid, then to p-toluate, and finally to terephthalate, eliminating the need for expensive petrochemical feedstocks and high-temperature oxidation processes.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent fundamentally changes the production parameters by shifting from high-temperature chemical oxidation (Mid Century Process) to mild physiological temperature biological synthesis. It replaces petrochemical para-xylene feedstock with renewable carbohydrate feedstocks, and uses engineered enzymatic pathways instead of cobalt/manganese catalyst systems, thereby reducing energy consumption and manufacturing costs.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If conventional p-xylene oxidation is used for PTA production, then product purity is achieved, but environmental sustainability is compromised

Engineering Contradiction:
Improveproduct purityVSAvoidenvironmental sustainability
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful dependence on petrochemical resources and high-energy oxidation processes into a beneficial renewable biological system. By engineering microorganisms to produce terephthalate from sugars through the shikimate pathway, it eliminates the need for para-xylene extraction from petroleum and high-temperature oxidation, thereby converting an environmentally harmful process into a sustainable one while maintaining product purity.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

Enables the cost-effective, renewable production of commercial quantities of p-toluate and terephthalate, overcoming the limitations of existing technologies by using engineered microbial organisms to convert carbohydrate feedstocks into these valuable compounds.

Implementation Method 1

utilizing enzymes like 2-dehydro-3-deoxyphosphoheptonate synthase and shikimate pathway enzymes to convert (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate to p-toluate

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

non-naturally occurring microbial organisms with engineered metabolic pathways to biosynthesize p-toluate and terephthalate from carbohydrate feedstocks

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS10385344B2Microorganisms and methods for the biosynthesis of (2-hydroxy-3methyl-4-oxobutoxy) phosphonate
Publication Date: 2019.08.20 GENOMATICA INC
  • US10385344B2 patent drawing
  • US10385344B2 patent drawing
  • US10385344B2 patent drawing

AI summary

The invention provides non-naturally occurring microbial organisms having a (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate pathway, p-toluate pathway, and/or terephthalate pathway. The invention additionally provides methods of using such organisms to produce (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate pathway, p-toluate pathway or terephthalate pathway.