Engineered Microbial Organisms for Adipate Biosynthesis
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Solution Overview
Problem
Current commercial processes for producing adipic acid and caprolactam are inefficient and require excessive oxidizing agents, necessitating the development of alternative biosynthetic methods for these commercially significant compounds.
Innovation Solution
Design and production of non-naturally occurring microbial organisms with engineered metabolic pathways to biosynthesize adipate, 6-aminocaproic acid, and caprolactam, utilizing pathways such as the reverse adipate degradation pathway and the 3-oxoadipate pathway, which allow for high yields without the need for oxygen and favorable energetics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current commercial oxidation processes are used to produce adipic acid and caprolactam, then production capability is achieved, but excessive oxidizing agents are required and process efficiency is low
Solution Approach 1:
The patent replaces chemical oxidation processes with biological fermentation processes. Specifically, it uses genetically engineered microorganisms (E. coli and S. cerevisiae) that express plant-derived enzymes (fumarylacetoacetate isomerase and enoyl-CoA hydratase) to convert fumarate into adipate and subsequently caprolactam through metabolic pathways, eliminating the need for excessive chemical oxidizing agents
Solution Approach 2:
The patent changes the fundamental production parameters from chemical oxidation conditions to biological fermentation conditions. This includes shifting from high oxidizing agent concentrations to controlled fermentation environments, from chemical catalysts to biological enzymes, and from oxidation reactions to metabolic conversion pathways, thereby improving efficiency and reducing substance loss
2Use of energy by moving object
If traditional biosynthetic pathways are used, then oxygen dependency increases and energetic requirements become excessive
Solution Approach 1:
The patent inverts the traditional approach by using reductive biosynthesis instead of oxidative pathways. The engineered microorganisms use reductive enzymes (enoyl-CoA hydratase and fumarylacetoacetate isomerase) to convert fumarate through a reductive pathway to adipate and caprolactam, thereby reducing oxygen dependency and lowering energetic requirements while maintaining high productivity
Solution Approach 2:
The patent introduces plant-derived enzyme intermediaries (fumarylacetoacetate isomerase from Arabidopsis thaliana and enoyl-CoA hydratase from Arabidopsis thaliana) that mediate the conversion of fumarate to adipate and caprolactam through alternative metabolic pathways, bypassing the need for oxygen-dependent steps and reducing overall energetic requirements
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 high yields of adipate and caprolactam with reduced energetic requirements and oxygen dependency, enabling efficient production of these compounds through microbial fermentation.
Implementation Method 1
The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective adipate, 6-aminocaproic acid or caprolactam pathway
Implementation Method 2
enabling efficient production of these compounds through microbial fermentation
Data Source
AI summary
The invention provides a non-naturally occurring microbial organism having an adipate, 6-aminocaproic acid or caprolactam pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective adipate, 6-aminocaproic acid or caprolactam pathway. The invention additionally provides a method for producing adipate, 6-aminocaproic acid or caprolactam. The method can include culturing an adipate, 6-aminocaproic acid or caprolactam producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an adipate, 6-aminocaproic acid or caprolactam pathway enzyme in a sufficient amount to produce the respective product, under conditions and for a sufficient period of time to produce adipate, 6-aminocaproic acid or caprolactam.