Recombinant Host Cell Lipid Metabolism Engineering
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Solution Overview
Problem
Current methods for improving protein yield in host cells, such as bacteria and fungi, face limitations in transcription, translation, protein folding, glycosylation, and secretion, leading to low production levels of proteins of interest, despite efforts like overexpressing chaperones and supplementing amino acids.
Innovation Solution
Engineering host cells to over- or underexpress polynucleotides encoding proteins involved in lipid metabolism, specifically altering sphingolipid and phospholipid biosynthesis, which modifies biomembrane lipid composition to enhance protein production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If transcription is enhanced by utilizing strong promoters or increasing the copy number of the heterologous gene, then protein yield is improved, but other bottlenecks downstream of transcription limit expression
Solution Approach 1:
The invention changes the biochemical parameters of the host cell by modifying lipid metabolism pathways. Specifically, it alters the composition of membrane lipids (sphingolipids and phospholipids) to improve protein expression efficiency, thereby addressing downstream bottlenecks without increasing genetic complexity
Solution Approach 2:
The invention introduces lipid metabolism proteins as intermediary elements that mediate between transcription and protein expression. By overexpressing proteins involved in lipid metabolism (such as LACS, FAD2, FAD3, FAE, and ELOVL), the system improves membrane properties and cellular conditions that facilitate protein expression downstream of transcription
2Productivity
If high level of protein yield is achieved in host cells, then production capacity is improved, but cell fitness decreases with decreased growth rate and biomass formation
Solution Approach 1:
The invention changes metabolic parameters by redirecting cellular resources toward lipid metabolism pathways. This alters the balance of cellular resources, allowing high protein yield to be achieved without the typical penalty of reduced cell fitness, as the lipid metabolism modifications create a more favorable cellular environment for both protein expression and cell growth
Data Source
AI summary
The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of expressing a protein of interest (POI) from a host cell. The invention relates particularly to improving a host cell's capacity to express and/or secrete a protein of interest and use of the host cell for protein expression. The invention also relates to cell culture technology, and more specifically to culturing cells to produce desired molecules for medical purposes or food products.