Microbial 1,3-BDO Production via Enzymatic Pathway Engineering

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Solution Overview

Problem

The existing methods for producing 1,3-butanediol rely on petroleum-based feedstocks, which are unsustainable and costly, and there is a need for a renewable and efficient biosynthetic route to produce this commodity chemical.

Innovation Solution

Engineering non-naturally occurring microbial organisms to express specific enzymes that catalyze the production of 1,3-butanediol through pathways involving alanine, acetoacetyl-CoA, and 4-hydroxybutyryl-CoA, optimizing fermentation conditions to achieve high yields and product formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If petroleum-based feedstocks (acetylene or ethylene) are used for producing 1,3-butanediol, then the production process is well-established and efficient, but the method becomes unsustainable and costly due to reliance on non-renewable resources

Engineering Contradiction:

Improveproduction efficiencyVSAvoidsustainability

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of feedstock type from petroleum-based (acetylene/ethylene) to renewable-based (glucose, xylose, arabinose, or syngas). This parameter change enables sustainability while maintaining production efficiency through optimized microbial pathways and fermentation conditions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the chemical synthesis mechanism (petrochemical conversion) with a biological mechanism (microbial fermentation). Engineered microorganisms convert renewable carbohydrates or syngas into 1,3-butanediol through metabolic pathways, substituting petroleum-based chemistry with renewable biology

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Device complexity

If traditional chemical synthesis pathways are used, then the process is simple and direct, but it relies on unsustainable petroleum feedstocks and produces harmful byproducts

Engineering Contradiction:

Improveprocess simplicityVSAvoidenvironmental harm

Core Design Contradiction:

Device complexityVSObject-generated harmful factors

Solution Approach 1:

The patent converts potentially harmful syngas components (CO, CO2, H2) into valuable 1,3-butanediol through engineered microbial pathways. The microorganisms utilize these gases as carbon and energy sources, transforming waste streams into useful products while minimizing environmental harm

Inventive Principle:

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

3Adaptability or versatility

If renewable feedstocks are used for 1,3-butanediol production, then sustainability is improved, but the production yield and efficiency may be reduced compared to petrochemical routes

Engineering Contradiction:

ImprovesustainabilityVSAvoidproduction yield

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent employs dynamic metabolic pathway engineering where microbial metabolism is optimized through controlled fermentation conditions, gene expression regulation, and pathway enhancement. This dynamic optimization achieves high yields from renewable feedstocks by adapting cellular metabolism to maximize 1,3-butanediol production

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent creates universal microbial platforms that can process multiple renewable feedstocks (glucose, xylose, arabinose, syngas) through engineered pathways. This multi-functionality allows the same microbial system to achieve high productivity across different renewable substrates, maintaining sustainability while ensuring efficient production

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

This approach enables the production of 1,3-butanediol with a high theoretical yield, providing a renewable and sustainable alternative to traditional methods, and allows for the subsequent production of butadiene in small facilities, reducing transportation risks and costs.

Implementation Method 1

The present invention satisfies this need and provides related advantages as well. In some embodiments, the present invention is directed to a non-naturally occurring microbial organism that includes a microbial organism having a 1,3-butanediol (1,3-BDO) pathway

Methodology Applied

Scientific EffectFermentation: Fermentation

Implementation Method 2

expressed in a sufficient amount to produce 1,3-BDO. The 1,3-BDO pathway includes an enzyme selected from the group consisting of a 2-amino-4-ketopentanoate (AKP) thiolase, an AKP dehydrogenase, a 2-amino-4-hydroxypentanoate aminotransferase

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS11708589B2Microorganisms for producing 1,3-butanediol and methods related thereto

Publication Date: 2023.07.25 GENOMATICA INC

AI summary

Provided herein is a non-naturally occurring microbial organism having a 1,3-butanediol (1,3-BDO) pathway and comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In some embodiments, the pathway includes reducing equivalents from CO or hydrogen. In certain embodiments, a 1,3-BDO pathway proceeds by way of central metabolites pyruvate, succinate or alpha-ketoglutarate. Also provided herein is a method for producing 1,3-BDO, includes culturing such microbial organisms under conditions and for a sufficient period of time to produce 1,3-BDO.