screening of huge libraries with 100% coverage
The SenseUp-Technology transforms your desired phenotype (e.g. production of a target molecule, presence of a new or altered catalytic activity) into a gradual optical signal and allows detection of the most beneficial clone under millions of others in minutes.
Common technology limits your screening to thousands of clones, making <1% of most libraries.
SenseUp screens 100% of your library, giving access to natures full bio-catalytical potential.
SenseUp develops genetically encoded sensors for your desired phenotype, which transform your target behavior (production of a specific molecule, presence of a specific enzymatic activity, secretion of a specific protein or peptide) into graded optical output. This enables use of flow-cytometry, which 1000x boosts the screening throughput and thus your chance, to find the desired clone in reasonable time.
Moreover, conventional screening is usually done from artificial lab-conditions (pH-buffered batch-process, low substrate- and product concentrations, shaking instead of stirring, …), limiting transferability of results into large-scale. The SenseUp-Technology enables screening from carefully monitored fermentation-conditions, mimicking real-world process-conditions and thus ensuring upscale-compatibility of results.
The real-time screen-capture below shows analysis of 10.000 cells per second. Each dot represents one analyzed cell. The further up in the plot a cell appears, the stronger the optical signal is and the more desired product is produced. The very best cells are directly isolated and spotted onto a 96-well plate.
In this experiment, SenseUp analyzed more than 1.000.000 microbial cells within the time you take for a coffee. Around 40 promising clones were isolated. There is a good chance, that one of them already supersedes our customers starting-strain, ready to boost his production process soon.
Our technology is applicable to all kinds of organisms, which are cultivatable under laboratory conditions. The biosensors are based on natural transcriptional regulators, giving access to a wide spectrum of sensor-specificities.
Biosensors for detection of nearly all industrially relevant amino acids (Arginine, Histidine, Lysine, Methionine, Threonine, Valine, Isoleucine, Leucine…) and many amino acid derivatives are available and successfully used to screen for enhanced production strains.
Biosensors indicating enhanced peptide- or protein-secretion by C. glutamicum or B. subtilis are available and successfully used to screen random libraries for expression and secretion of difficult-to-express peptides or proteins such as human peptide-hormones or antibodies.
Biosensors for monitoring cofactor-consumption in E. coli are available and used to screen for new or improved catalytic activities of NAD(P)-dependent enzymes.
Biosensors for many other small molecules are available and applicable to screen for desired pathways or enzymes in metagenome-libraries.
Natural evolution of a Corynebacterium glutamicum
strain with the SenseUp-Technology.
Aim: Identification of L-Lysine producing clones showing
increased productivity under process conditions.
In this project we doubled the productivity of a non-GM C. glutamicum L-Lysine production strain by eight enrichments of 100.000 promising clones in each step. The screening-steps took about 2 hours each, followed by two days of cultivation.
After two weeks, 96 single cells were isolated and analyzed individually. About 70% of them showed increased productivity, three of them about 2x fold.
In these cases, the genome sequence unraveled the duplication of a large genomic fragment, containing (amongst others) operons of the pentose-phosphate-pathway.
Identifying new targets for
L-Lysine production in
with the SenseUp-Technology
Aim: Identification of novel mutations leading to L-Lysine formation.
We performed random mutagenesis of wild type cells and screened about 10.000.000 cells with our lysine-sensor.
Around 40 promising clones were isolated and analyzed by whole genome sequencing, resulting in identification of more than 150 mutations.
After re-engineering using multiplex-genome-engineering combined with the SenseUp-Technology, novel mutations for overproduction of lysine were identified and patented.