Genetically Engineered Microorganism for PDO BDO PHP Production
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Solution Overview
Problem
Current methods for producing 1,3-propanediol (PDO) by fermentation face challenges such as cell growth arrest, reduced PDO yield, lactic acid accumulation, and insufficient intracellular Coenzyme NADH2, leading to increased production costs and difficulties in industrial-scale production.
Innovation Solution
A genetically engineered micro-organism is developed by deleting the D-lactate dehydrogenase gene and introducing Coenzyme A-dependent Aldehyde dehydrogenase and Polyhydroxyalkanoate synthase genes, allowing for increased NADH2 synthesis, reduced lactic acid production, and enhanced yields of PDO and BDO, along with the production of polyhydroxypropionic acid (PHP), through fed-batch fermentation with glycerol and an alkali solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional synthesis method is used to produce PDO from ethylene oxide or propylene, then PDO can be produced, but the process suffers from severe operation conditions of high temperature and high pressure, multiple undesired byproducts, unsatisfactory selectivity, and huge investment on installations
Solution Approach 1:
The patent replaces the traditional chemical synthesis method (mechanical/chemical system requiring high temperature, high pressure, and complex installations) with a biological fermentation system using genetically engineered microorganisms. This substitution eliminates the need for severe operation conditions and complex equipment while maintaining PDO production capability.
Solution Approach 2:
The patent changes the production parameters from extreme conditions (high temperature, high pressure) to mild fermentation conditions by using genetically engineered microorganisms. The genetic modifications alter the metabolic pathways to favor PDO production under gentle biological conditions, thereby reducing equipment complexity and investment.
2Ease of operation
If PDO fermentation production method is used, then selectivity and mild operation conditions are achieved, but cell growth arrest, reduced PDO yield, lactic acid accumulation, and insufficient intracellular Coenzyme NADH2 occur
Solution Approach 1:
The patent segments the metabolic pathways by specifically modifying individual genes (ldhA, pta, ackA, frdA) to control different metabolic fluxes. This segmentation allows independent optimization of lactic acid production, PDO production, and NADH2 regeneration, resolving the contradiction between mild operation conditions and high productivity.
Solution Approach 2:
The patent introduces an intermediary mechanism through the pta-ackA pathway modification, which mediates the conversion of phosphoenolpyruvate to acetyl-CoA, thereby regulating both PDO production and NADH2 availability. This intermediary pathway resolves the conflict between maintaining mild fermentation conditions and achieving high PDO yield.
3Quantity of substance
If BDO is produced as a byproduct of PDO fermentation, then BDO can be obtained, but its yield is relatively low and it is generally not isolated and purified
Solution Approach 1:
The patent converts the previously unwanted BDO byproduct into a valuable co-product by engineering the microorganism to produce both PDO and BDO in significant quantities. The genetic modifications that optimize PDO production simultaneously enhance BDO formation, turning a waste stream into an additional revenue source and improving overall process efficiency.
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 results in increased PDO and BDO yields, decreased lactic acid production, and improved raw material utilization efficiency, lowering production costs and facilitating the isolation of desired products.
Implementation Method 1
Methods for the combined production of 1,3-propanediol (PDO), 2,3-butanediol (BDO), and polyhydroxypropionic acid (PHP) by fermentation
Data Source
AI summary
The present invention relates to genetically engineered micro-organisms for the combined production of 1,3-propanediol (PDO), 2,3-butanediol (BDO), and polyhydroxypropionic acid (PHP) by fermentation. In particular, the invention relates to a genetically engineered micro-organism suitable for combined production of PDO, BDO and PHP by fermentation, characterized in that: compared with corresponding wild-type starting micro-organism, the D-lactate dehydrogenase gene in the genetically engineered micro-organism is deleted or functionally inactivated, and the genetically engineered micro-organism comprises a heterogenous polynucleotide encoding the Coenzyme A-dependent Aldehyde dehydrogenase and a heterogenous polynucleotide encoding the Polyhydroxyalkanoate synthase. Methods for the construction of such micro-organisms, and methods for combined production of PDO, BDO and PHP by fermentation of a genetically engineered bacterium are also taught.