ENGINEERS at Washington University, US, have engineered a ‘population quality control’ (PopQC) tool which kills bacterial cells with low productivity, boosting production rates of biologically-produced products, the researchers say.
As scientists seek sustainable, bio-based alternatives to petrochemical fuels, chemicals and pharmaceuticals, they are increasingly turning to genetically engineered microbes. The engineering process increases the productivity of a specific substance. However, even in a population of genetic clones, non-genetic biological variation, or ‘noise’, means that some bacteria do not produce large quantities of the desired substance and simply consume nutrients. Washington assistant professor of energy, environmental & chemical engineering Fuzhong Zhang developed the PopQC tool to identify and kill off these ‘lazy’ cells, leaving behind only the highest producers.
PopQC, for which Zhang has applied for a patent, is an intracellular biosensor that responds to the relative abundance of a specific product. The team tested their system on two genetically engineered strains of Escherichia coli bacteria, both containing the biosensor. The strains, respectively, produced free fatty acids, a precursor for biofuels and some high-volume chemicals, and tyrosine, an amino acid used as a precursor to pharmaceuticals.
Both strains of bacteria contained a gene which makes a protein controlling the passage of the antibiotic tetracycline through the bacterial cell wall. Using artificial promoters, Zhang connected the expression of the gene to the PopQC biosensor. When PopQC detects larger quantities of either free fatty acids or tyrosine, it activates the gene, producing the protein. When the researchers then added tetracycline, bacteria producing large quantities of the desired product could pump the antibiotic out of their cells and survive. In low-producing, or lazy bacteria, the gene was not activated, meaning these cells could not pump the antibiotic out of their cells and died.
The engineered cell lines with PopQC produced three times as much tyrosine and free fatty acids as those without PopQC, as the hard-working cells dominated the culture.
“PopQC could be applied to a variety of biosynthetic pathways and host organisms as long as a proper sensor exists that detects the product in the engineered host,” said Zhang. “Because noise is a universal problem in biology, the design principle of this work should inspire engineers from many other fields to improve efficiency of engineered systems.”
Nature Chemical Biology DOI: 10.1038/nchembio.2046
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