Menu


Every cell is different





Learn More

Enhancing large-scale bioproduction

Ensuring homogeneity of cultivated populations in large-scale bioprocesses will lead to significant increases in product yield and titer.


Heterogeneity increases with rising cell generations.
With product addiction we apply groundbreaking proprietary technology to radically optimize production strain performance in large-scale bioproduction. This not only ensures higher yields, but allow for a palette of additional benefits.

Our Approach

In short time, we enhance production yields by addressing strain heterogeneity in four steps:

Subpopulations

1. Population health check

Using proprietary deep-seq technology, we start by performing population health checks and analysis of strain stability. We map out the genetic paths of production escape, and create the layout for genetic engineering solutions.

2. Baseline profiling

We profile the target strain at production-mimicking conditions to correlate detected heterogeneities with performance.

3. Addiction to product

Using our proprietary technology, we addict the cells in the population to product. This leads to a homogenous fermentation population of high-producing cells and thereby to higher production. Our population technologies can be applied at many process stages, to enable or speed up development or improve already commercialized fermentation.

4. Test with client and final delivery

We evaluate the performance improvement and potential for further engineering. At maximum production performance, the strain will be transferred to client pilot plant facilities for final test and implementation.



Benefits

Higher
yield
Enable
toxic processes
Antibiotic independenceHomogenous protein
By retaining only high-producing cells in the fermentation population we are able to increase yields and titer.Product addiction minimizes the selective development of non-producing subpopulations at fermentation scale. This enables scale-up of difficult and toxic processes.Our designs are free from antibiotic resistance genes, easing downstream handlingFor protein production, we reduce the risk of heterogenous product formation


Compatible

Product
agnostic
Organism
agnostic
No or limited foreign genetic material
Our technology can be applied to protein and metabolite products.Approval is straight forward for existing processes.Our designs are free from antibiotic resistance genes, easing downstream handling

Partnering model

Flexible partnership

We offer flexible partner models that allow you to move fast forward and retain ownership.

Fast and responsive

Experts in scale-up genetics, we can check and fine-tune your strain to your process in short time.

Safety adapted to you

We understand the importance of conforming to desired data safety regulations and regulatory requirements.

Testimonials

Heterogeneity in Bacterial Protein Production


Technology of Enduro Genetics has been demonstrated in the commercial process of Aquaporin A/S, a Danish manufacturer of sustainable water filter solutions.

Copenhagen, Denmark, January 2019
In a first-of-its-kind study, the biotech start-up Enduro Genetics first applied its proprietary sequencing algorithm to detect and quantify heterogeneity in the populations of industrial 200-L protein fermentations and next optimize the fermentation organism to increase production. Enduro Genetics analysed time-lapse samples from the fermentation process and identified a 4-5 percent selective enrichment of mutated sub-populations within 200-L fermentation processes at Aquaporin A/S, a manufacturer of sustainable water filter solutions. The details of the identified heterogeneity is kept confidential, but are of a type that leads to lowered production without influencing the product quality.

Recognizing cellular variation Enduro Genetics improved production
Enduro Genetics holds a proprietary technology platform to optimize fermentation processes ensuring a uniform population, consisting of highly productive cells. In collaboration with Aquaporin A/S, Enduro Genetics re-engineered the production strain. The new production strain performed at least 45 percent better in lab-scale tests (Fig. 1).

Vice President of Membrane Protein Production at Aquaporin A/S, Torsten Bak says:
Fig. 1. In the collaboration, specific production of the Aquaporin production strain was improved by Enduro Genetics. Error bars depict s.e.m. (n = 3).

In their designs, Enduro Genetics optimizes towards ensuring a more homogenous production population with evolutionary incentives for high production and evolutionary penalties for low production. This new design means that cells will remain productive or even increase production. Importantly, all Enduro Genetics's solutions are free from antibiotic resistance genes and other foreign genes. This freedom improves the environmental profile of the fermentation process and eliminates the use of antibiotics that has long been a downside of many biotechnological production processes.

Important industrial tech validation

The potential for using heterogeneity as optimization target in industrial fermentation has been speculated in several recent academic publications (e.g. Rugbjerg et al, 2018). However, genetic instability in populations of engineered production organisms is difficult to detect and quantify as mutation can be challenging to distinguish from technical sequencing noise. The potential loss of product is therefore difficult to quantify. says CEO and co-founder of Enduro Genetics, Peter Rugbjerg.

Proprietary algorithm boosts productivity of industrial fermentation process
Analyzing two fermentation batches Enduro Genetics applied its algorithm to identify 4 % and 5 % enriched subpopulation mutated in key production genes, for each process (Fig. 2). says CTO and co-founder of Enduro Genetics, Christian Munck.



Fig. 2. Enrichment in the fermentation population of a particular genetic escape cell mutated in a key production gene during 200-liter commercial fermentation, from below 0.1% to 4-5 % frequency detected using deep-sequencing.

While the mutated subpopulation represented less than 0.1 % of the population following 22 hours of fermentation, this number rose to 4 and 5 %, for each process, at the end of the fermentation process.

Aquaporin A/S produces its innovative active ingredient the aquaporin using an engineered bacterial strain and is working continuously to optimize and streamline its processes, pushing for better and more efficient production.

High cellular burden from elevated production can easily lead to declining performance. Enduro Genetics's Population Health Check is a first powerful step to improve the genetic homogeneity within a biological process and provide valuable candidate targets for production optimization.

A Population Health Check can be completed in 2 weeks and only requires time-resolved, isolated DNA from the bioreactor culture.

Follow us on LinkedIn or Twitter to stay updated.



Publications

Enduro Genetics technology works off from the following public articles:

Rugbjerg et al, 2018. Diverse Genetic Error Modes Constrain Biological Production, Nature Communications

WO2017055360A1 A System For Improved Fermentation Titers

Enduro Genetics

Managing team

Peter Rugbjerg, PhD. CEO
Christian Munck, PhD. CTO

Vision

Relying on living organisms, bioproduction is inherently victim to the whims of nature. By applying game-changing synthetic biological technology, we empower our partner companies to maximize performance of all cells cultivated from their production strains. By changing the desire of cells to produce, we increase competitiveness of current and future green bioproduction.

Mission

Based in Copenhagen, Denmark, Enduro Genetics is an independent service and tech provider committed to improving large-scale fermentations.

Learn more

Contact us at info@endurogenetics.com or +45 93 93 55 80.