Redirecting Malonyl-CoA Flux in Engineered Microorganisms
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Solution Overview
Problem
Current methods for renewable production of fuels and industrial chemicals face challenges in increasing rate, productivity, and cost-effectiveness for biosynthesis of chemical products, particularly in reducing the conversion of malonyl-CoA to fatty acids in microorganisms.
Innovation Solution
Genetically modifying microorganisms, such as E. coli, by reducing enzymatic activity in fatty acid synthase pathway enzymes and introducing modifications to increase metabolic production pathways from malonyl-CoA, allowing for the production of various chemicals like butanol, 3-hydroxypropionic acid, and fatty acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If microorganisms are used for renewable production of fuels and chemicals, then sustainable production is achieved, but the rate, productivity, and cost-effectiveness of biosynthesis are insufficient
Solution Approach 1:
The patent applies parameter changes by genetically modifying enzyme parameters in the fatty acid synthase pathway. Specifically, it reduces the enzymatic activity of key enzymes (beta-ketoacyl-ACP synthase, enoyl-ACP reductase, malonyl-CoA-ACP transacylase) to alter metabolic flux parameters, thereby increasing productivity of target chemicals while improving cost-effectiveness through optimized resource utilization.
Solution Approach 2:
The patent extracts or removes the competing fatty acid synthesis pathway by reducing enzymatic activity of FAS pathway enzymes. This extraction of the competing pathway redirects carbon flow from fatty acid production to the desired chemical production pathway, thereby improving both productivity and cost-effectiveness of the target biosynthesis process.
2Quantity of substance
If microorganisms naturally convert malonyl-CoA to fatty acids, then fatty acid production occurs, but carbon flow is diverted away from desired chemical products
Solution Approach 1:
The patent extracts or removes the competing fatty acid synthesis pathway by reducing enzymatic activity of FAS pathway enzymes. This extraction of the competing pathway redirects carbon flow from fatty acid production to the desired chemical production pathway, thereby improving both productivity and cost-effectiveness of the target biosynthesis process.
Solution Approach 2:
The patent inverts the natural metabolic flow by suppressing the default fatty acid synthesis pathway and redirecting carbon flow toward alternative chemical products. Through genetic modification of FAS enzymes, the metabolic flux is reversed from the natural pathway toward engineered product synthesis pathways.
Data Source
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AI summary
Metabolically engineered microorganism strains are disclosed, such as bacterial strains, in which there is an increased utilization of malonyl-CoA for production of a chemical product. Such chemical products include polyketides, 3-hydroxypropionic acid, and various other chemical products described herein. Methods of production also may be applied to further downstream products, such as consumer products. In various embodiments, modifications to a microorganism and/or culture system divert, at least transiently, usage of malonyl-coA from the fatty acid biosynthesis pathway and thereby provides for usage of the malonyl-coA for a chemical product other than a fatty acid. In various embodiments, the fatty acid biosynthesis pathway is modulated to produce specific fatty acids or combinations of fatty acids.