Decoupling Microbial Growth from Biochemical Production
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Solution Overview
Problem
Current methods for producing biochemical compounds like L-tyrosine and mevalonate, and recombinant polypeptides in microorganisms face challenges in achieving high yields due to the coupling of cell growth and production processes, leading to inefficient use of feedstock and reduced biochemical output.
Innovation Solution
Decoupling cell growth from production by downregulating nucleotide biosynthesis in microorganisms, specifically by inhibiting the expression or activity of enzymes involved in nucleotide biosynthesis, allowing for increased production of biochemical compounds and recombinant polypeptides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cell growth is promoted in microorganisms, then biomass production increases, but biochemical compound yield decreases due to feedstock being consumed for biomass formation
Solution Approach 1:
The patent extracts and eliminates the harmful coupling between cell growth and biochemical production by targeting and inhibiting specific nucleotide biosynthesis enzymes (such as orotidine-5'-phosphate decarboxylase, carbamoyl phosphate synthase, or aspartate carbamoyltransferase). This selective inhibition removes the resource competition between biomass formation and biochemical production, allowing feedstock to be redirected toward biochemical compound synthesis.
Solution Approach 2:
The patent changes the metabolic parameter of nucleotide biosynthesis by downregulating specific enzymatic steps through genetic modification or enzymatic inhibition. This parameter change shifts the metabolic flux from biomass formation pathways to biochemical production pathways, resolving the contradiction between cell growth and biochemical yield.
2Productivity
If nucleotide biosynthesis is downregulated to control cell growth, then biochemical production increases, but cell growth is reduced
Solution Approach 1:
The patent extracts the growth control function from the overall metabolism by specifically targeting nucleotide biosynthesis enzymes. This selective extraction allows independent control of growth and production, where growth is limited only when necessary, while production pathways remain active and optimized.
Solution Approach 2:
The patent segments the metabolic network into growth-related pathways (nucleotide biosynthesis) and production-related pathways (biochemical synthesis). By independently regulating these segmented pathways through specific enzyme inhibition, the system can optimize each function separately without compromising the other.
3Quantity of substance
If feedstock is allocated to cell growth, then microbial biomass increases, but biochemical compound production yield decreases
Solution Approach 1:
The patent extracts the feedstock consumption that would otherwise be dedicated to nucleotide biosynthesis and redirects it toward biochemical compound production. By inhibiting nucleotide biosynthesis enzymes, the system extracts this resource from the biomass formation pool and allocates it to the production pool, improving overall feedstock efficiency.
Solution Approach 2:
The patent changes the metabolic parameter of feedstock allocation by downregulating nucleotide biosynthesis. This parameter change shifts the distribution of feedstock from biomass formation to biochemical production, optimizing the use of available resources and reducing waste.
Data Source
AI summary
The present invention generally relates to industrial microbiology, and specifically to the production of biochemical compounds, such as L-serine, L-tyrosine, mevalonate and their derivatives, and recombinant polypeptides using genetically modified microorganisms. More particularly, the present invention pertains to the decoupling of cell growth from production of biochemical compounds, such as L-serine, L-tyrosine, mevalonate and their derivatives, in a microorganism by down regulating the nucleotide biosynthesis in said microorganism.