Genetically Modified Microbes for 1,4-Butanediol Biosynthesis

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Solution Overview

Problem

Current methods for producing 1,4-butanediol rely on petroleum-based feedstocks and energy-intensive processes, with succinic acid being costly and difficult to isolate, necessitating alternative means for efficient production.

Innovation Solution

Design and production of non-naturally occurring microbial organisms with optimized 1,4-butanediol pathways, including specific enzymes and genetic modifications, to biosynthesize 4-hydroxybutanoic acid and downstream products like 1,4-butanediol, utilizing in silico models and recombinant engineering.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If petroleum-based feedstocks (acetylene, maleic anhydride, propylene oxide) are used for 1,4-butanediol production, then current industrial production can be maintained, but reliance on non-renewable resources and energy-intensive processes continues

Engineering Contradiction:
Improve1,4-butanediol production efficiencyVSAvoidfeedstock sustainability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of feedstock type from petroleum-based (acetylene, maleic anhydride, propylene oxide) to renewable biomass-based substrates. This parameter change enables sustainable production while maintaining productivity through engineered microbial pathways that convert biomass into 1,4-butanediol and its derivatives.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional chemical catalysis and high-temperature/pressure processing with biological catalysis using engineered microorganisms. The microbial systems naturally perform the chemical transformations at mild conditions, substituting mechanical and thermal energy inputs with biochemical pathways.

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

2Adaptability or versatility

If succinic acid is used as an intermediate for butanediol production, then renewable feedstock can be utilized, but isolation and purification costs increase and high temperatures and pressures are required for catalytic reduction

Engineering Contradiction:
Improverenewable feedstock utilizationVSAvoidenergy consumption for catalytic reduction
Core Design Contradiction:
Adaptability or versatilityVSUse of energy by stationary object

Solution Approach 1:

The patent extracts and eliminates the problematic intermediate step involving succinic acid isolation, purification, and high-energy catalytic reduction. Instead, the engineered microbial pathways directly produce 1,4-butanediol or its precursors (4-hydroxybutanoic acid, γ-butyrolactone) from renewable feedstocks, bypassing the energy-intensive succinic acid processing step entirely.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary genetic engineering of microorganisms to establish complete biosynthetic pathways before substrate introduction. The microbes are pre-programmed with all necessary enzymes and metabolic routes to efficiently convert renewable feedstocks into target products, avoiding the need for subsequent high-energy chemical processing steps.

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If conventional chemical synthesis methods are used, then established industrial processes can be maintained, but energy consumption and capital intensity increase

Engineering Contradiction:
Improveprocess establishmentVSAvoidenergy consumption
Core Design Contradiction:
Ease of manufactureVSUse of energy by stationary object

Solution Approach 1:

The patent replaces energy-intensive chemical synthesis equipment and high-temperature/pressure reactors with simple fermentation vessels containing engineered microorganisms. The biological systems perform complex multi-step chemical transformations under ambient conditions, eliminating the need for expensive and energy-intensive industrial chemical processing equipment.

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

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

Achieves efficient and cost-effective production of 1,4-butanediol by using genetically modified microbes, reducing reliance on petroleum-based sources and energy consumption, while stabilizing genetic alterations for continuous bioprocesses.

Implementation Method 1

The engineered microbes contain a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme

Methodology Applied
Scientific EffectEnzymatic reactions: Enzyme

Implementation Method 2

methods of using such microbial organisms to produce BDO

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentEP4056706A1Microorganisms for the production of 1,4-butanediol and related methods
Publication Date: 2022.09.14 GENOMATICA INC
  • EP4056706A1 patent drawingFigure 1
  • EP4056706A1 patent drawingFigure 2
  • EP4056706A1 patent drawingFigure 3(a)~3(c)

AI summary

The invention provides non-naturally occurring microbial organisms comprising a 1,4-utanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO.