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 non-naturally occurring microbial organisms with engineered pathways for 4-hydroxybutanoic acid, 4-hydroxybutanal, 4-hydroxybutyryl-CoA, and putrescine biosynthesis, using exogenous nucleic acids to express enzymes that enable efficient production of these compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If petroleum-based feedstocks are used for 1,4-butanediol production, then production scale and market supply are maintained, but energy consumption and capital investment increase
Solution Approach 1:
The patent replaces conventional petrochemical mechanical/thermal processes with biological fermentation processes. Microorganisms are engineered to metabolize renewable feedstocks and produce 1,4-butanediol through biochemical pathways, substituting high-energy petrochemical synthesis with lower-energy biological conversion
Solution Approach 2:
The patent changes the fundamental production parameters by shifting from petrochemical feedstocks to renewable biomass feedstocks. This parameter change enables production under milder conditions (ambient temperature and pressure) compared to high-temperature petrochemical processes, thereby reducing energy consumption
2Adaptability or versatility
If succinic acid is used as biologically-produced intermediate, then renewable feedstock substitution is achieved, but production cost increases due to isolation and purification requirements
Solution Approach 1:
The patent extracts the desired product (1,4-butanediol) directly from the fermentation broth through engineered microbial pathways, eliminating the need for complex isolation and purification of intermediate compounds like succinic acid. The metabolic pathway is designed to produce the final product directly, simplifying downstream processing
Solution Approach 2:
The patent uses engineered microbial cells as living factories that serve as intermediaries between renewable feedstocks and the target product. These microorganisms contain optimized metabolic pathways that directly convert feedstock to 1,4-butanediol, eliminating the need for separate isolation and chemical conversion steps required when using succinic acid as an intermediate
3Adaptability or versatility
If succinic acid is used as intermediate, then biological production pathway is established, but high temperatures and pressures are required for catalytic reduction
Solution Approach 1:
The patent replaces high-temperature catalytic reduction with biological reduction pathways. Engineered microorganisms use enzymatic systems to reduce intermediates to 1,4-butanediol under mild physiological conditions, substituting high-temperature chemical processes with low-temperature biological processes
Solution Approach 2:
The patent changes the processing temperature parameter by utilizing biological systems that operate at ambient or physiological temperatures. The engineered metabolic pathways enable product formation under mild conditions, eliminating the need for high-temperature catalytic reduction required by conventional chemical methods
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
The microbial organisms produce 1,4-butanediol and its precursors with reduced energy and capital requirements, offering a sustainable alternative to petroleum-based methods and improving production efficiency.
Implementation Method 1
comprising at least one exogenous nucleic acid encoding a BDO, 4-HBal and/or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-HBal, 4-HBCoA and/or putrescine
Data Source
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.