Engineered Microbial Pathways for 1,4-Butanediol Production

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Solution Overview

Problem

Current methods for producing 1,4-butanediol and its precursors are energy- and capital-intensive, relying on petroleum-based feedstocks, and alternative biologically-produced intermediates like succinic acid are costly and require high temperatures and pressures.

Innovation Solution

Design and production of microbial organisms with engineered biosynthetic pathways for 4-hydroxybutanoic acid, 4-hydroxybutanal, 4-hydroxybutyryl-CoA, and putrescine production, using nucleic acids encoding specific enzymes to express these pathways in organisms like E. coli, optimizing their expression for efficient production.

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 production capacity and established industrial processes are maintained, but energy consumption and capital investment are high

Engineering Contradiction:
Improve1,4-butanediol production capacityVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent replaces conventional petrochemical mechanical/thermal processes with biological enzymatic processes. Microorganisms equipped with engineered metabolic pathways convert renewable feedstocks (glucose, starch, cellulose) to 1,4-butanediol through biological metabolism, substituting high-energy chemical synthesis and catalytic hydrogenation with lower-energy biological conversion

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

Solution Approach 2:

The patent changes the fundamental parameters of the production system by shifting from petroleum-based feedstocks to renewable biomass feedstocks, and from high-temperature/pressure chemical processes to ambient-temperature biological processes. This parameter change enables reduced energy consumption while maintaining productivity

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If succinic acid is produced biologically as an intermediate, then renewable feedstock substitution is achieved, but isolation and purification costs are high and high temperatures and pressures are required for catalytic reduction

Engineering Contradiction:
Improverenewable feedstock substitutionVSAvoidisolation and purification cost
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent extracts the problematic intermediate step (succinic acid isolation and purification) from the overall process by engineering microorganisms to directly produce 1,4-butanediol through a complete metabolic pathway. This eliminates the need for separate purification and high-energy reduction steps, achieving renewable feedstock substitution while simplifying manufacturing

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses engineered microorganisms as living intermediaries that perform the complete conversion from renewable feedstocks to 1,4-butanediol in a single integrated biological system, replacing the multi-step chemical process involving succinic acid isolation, purification, and high-energy catalytic reduction

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional petrochemical processes are used, then established industrial infrastructure is utilized, but the process is capital-intensive

Engineering Contradiction:
Improveindustrial process stabilityVSAvoidcapital investment
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces capital-intensive petrochemical infrastructure with biological manufacturing systems. Microorganisms serve as biocatalysts in fermentation processes that can be conducted in simple bioreactors using renewable feedstocks, eliminating the need for expensive petroleum refining and high-energy chemical processing infrastructure

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

Facilitates the production of 1,4-butanediol and its precursors using renewable feedstocks, reducing energy and capital requirements, and enhancing production yields through adaptive evolution and optimized metabolic designs.

Implementation Method 1

The invention provides non-naturally occurring microbial organisms containing a 1,4-butanediol (BDO), 4-hydroxybutanal (4-HBal), 4-hydroxybutyryl-CoA (4-HBCoA) and/or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-HBal and/or putrescine pathway enzyme

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS11572564B2Microorganisms for producing 1,4-butanediol and methods related thereto
Publication Date: 2023.02.07 GENOMATICA INC
  • US11572564B2 patent drawing
  • US11572564B2 patent drawing
  • US11572564B2 patent drawing

AI summary

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