Biosynthesizing C7 Building Blocks from Chorismate
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Solution Overview
Problem
There is a need for economically viable methods to produce the monomers for novel polyamides, such as Nylon 7 and Nylon 7,7, as existing petrochemical routes are not economically feasible, and wild-type microorganisms do not naturally overproduce or excrete the required C7 building blocks like pimelic acid, 7-aminoheptanoate, 7-hydroxyheptanoate, heptamethylenediamine, and 1,7-heptanediol.
Innovation Solution
The development of biochemical pathways using isolated enzymes or recombinant host cells to biosynthesize these C7 building blocks from chorismate, benzoyl-CoA, or benzoate, involving enzymes like dehydrogenases, reductases, hydrolases, and CoA-ligases, and cultivating under specific conditions to direct carbon flux towards these compounds, overcoming the optimality principle and natural production limitations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If petrochemical routes are used to produce C7 building blocks, then production can proceed with existing infrastructure, but the process is not economically viable
Solution Approach 1:
The patent replaces petrochemical mechanical/chemical processes with biocatalytic enzymatic processes. Specifically, it uses engineered biochemical pathways in microorganisms to convert renewable feedstocks (sugars, starches, cellulose) into C7 building blocks through enzymatic reactions, substituting the traditional petrochemical refining and synthesis processes with biologically-based transformations that are more economically viable and environmentally sustainable
Solution Approach 2:
The patent changes the fundamental parameters of the production system by shifting from fossil-based feedstocks to renewable biological feedstocks, and from high-temperature/pressure petrochemical processes to mild-condition enzymatic processes. This includes changing the catalyst type (from metal catalysts to enzymes), reaction conditions (from harsh to mild), and feedstock source (from petroleum to biomass), thereby achieving economic viability through parameter optimization
2Reliability
If wild-type microorganisms are used, then natural metabolic pathways are maintained, but C7 building blocks are not overproduced or excreted
Solution Approach 1:
The patent segments the metabolic pathway into discrete enzymatic steps and individually optimizes each step. It introduces separate heterologous genes encoding specific enzymes (such as acetyl-CoA synthetase, acetate kinase, and phosphotransacetylase) to create a dedicated C7 building block production pathway that is independent from and does not interfere with the host's native metabolic pathways, thereby maintaining metabolic stability while achieving high productivity
Solution Approach 2:
The patent employs universal enzyme systems that can process multiple substrates and produce multiple products. The engineered pathways use promiscuous enzymes capable of handling various feedstock-derived intermediates and directing carbon flux toward C7 building blocks while still allowing the host organism to maintain its essential metabolic functions for growth and survival
3Productivity
If carbon flux is directed towards C7 building blocks, then production of target compounds increases, but biomass growth is reduced due to the optimality principle
Solution Approach 1:
The patent introduces intermediary metabolic nodes and shuttle systems that allow carbon to be diverted to C7 building block production and then returned to central metabolism. These intermediaries act as buffers that decouple product synthesis from growth metabolism, enabling the cell to maintain biomass production while simultaneously channeling carbon flux toward target compound synthesis through separate, parallel pathways
Solution Approach 2:
The patent implements preliminary metabolic preparation by pre-loading the system with essential precursors and cofactors needed for both growth and product synthesis. The engineered pathways are designed to operate in a manner that prepares metabolic intermediates in advance, allowing the organism to maintain growth while having ready-access carbon pools available for C7 building block production, thereby reducing the trade-off between growth and productivity
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 allows for efficient production of C7 building blocks by constructing non-natural pathways and manipulating host microorganisms, enabling the synthesis of pimelic acid, 7-aminoheptanoate, 7-hydroxyheptanoate, heptamethylenediamine, and 1,7-heptanediol, which are crucial for forming terminal functional groups in these polyamides.
Implementation Method 1
Biocatalysis is the use of biological catalysts, such as enzymes, to perform biochemical transformations of organic compounds
Implementation Method 2
enzymes like dehydrogenases, reductases, hydrolases, and CoA-ligases
Implementation Method 3
enzymes like dehydrogenases, reductases, hydrolases, and CoA-ligases
Data Source
AI summary
This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoate, 7-hydroxyheptanoate, heptamethylenediamine, or 1,7-heptanediol by forming two terminal functional groups, comprised of carboxyl, amine or hydroxyl group, in a C7 aliphatic backbone substrate produced from chorismate or benzoate. These pathways, metabolic engineering and cultivation strategies described herein rely on the anaerobic benzoyl-CoA degradation pathway enzymes.