EV Biotech creates microbial cell factories (MCF) for industrial production of high-value chemicals and proteins

 

With our computational pipeline we create MCFs faster and more effectively than the common trial-and-error lab methods.

 

Our main hosts are E. coli, B. subtilis, and S. cerevisiae, but can use other hosts if required for a specific product.

1. Research

We perform a comprehensive search of the scientific literature and patents on the compound of interest complemented with market research, providing a realistic view of the technological and market options in the earliest development stage.

Benefits

Deep and detailed study of scientific literature and patents, production and purification methods and market potential of the compound of interest

Transformation of an idea into a concept, with defined modelling and lab strategies and technological challenge identification for thorough assessment of the technological and commercial potential

Frequently Asked Questions

Why does the research stage require so much time?

The short answer: because it pays off. The comprehensive research saves a lot of time on the subsequent development steps. We study biotechnological, IP and market aspects of the compound of interest and its production method. As a result, we suggest only the most promising approaches for further consideration.

What is your research team’s background?

Our multidisciplinary team covers a broad range of expertise including plant biochemistry, microbial science, medical biology, computational biology and protein engineering. This background variety allows us to look at your request from very different angles and find innovative out-of-box solutions.

We have some data that can help you with research and modelling. How can we be sure about data safety?

All our data are stored in closed systems. We provide a data management plan as part of the confidentiality agreement. Our CTO also acts as our digital safety officer and she is happy to answer questions about specific concerns.

Does EV Biotech develop MCF strains on demand?

Yes we do. We welcome requests for co-development projects. Our core activities comprise three phases: 1. Research and modelling, 2. Engineering and optimization, 3. Handover. This three-phase pipeline for strain engineering forms the basis for the conditions of the partnership. When the MCF has been delivered, we offer additional support services for upscaling, implementation and strain maintenance on a fee-for-service basis.

Why isn’t metabolic modelling widely used by Industry?

Metabolic modelling is a young technology, for which only recently sufficient computational power has become available. Big players would require a disproportionate amount of investment to launch a functional modelling department. We are here to serve them. Our small yet multidisciplinary team has all necessary knowledge and the benefit of direct contact and easy collaboration between wet and dry lab.

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2. Development / Modelling

Using cutting-edge scientific developments in systems biology, we create in-house computational models of microorganisms for rational prediction of the genetic modifications required for production of the compound of interest.

Benefits

Replacing lab work with virtual experiments saves time and valuable resources, and also helps to discover the less obvious roads that are actually easier to travel

Identification of the most (cost-)effective organism and culture conditions without the need to try them all

Frequently Asked Questions

How reliable are the in-silico experiment predictions?

The predictions are not 100% reliable, but can exclude the vast majority of unsuccessful cases. Moreover, our digital test system is self-learning. The data generated by the subsequent wet lab work are fed back into the system and are used for further model optimization.

What kind of digital experiments can you carry out?

The whole spectrum from whole organism flux balance analyses to protein engineering using molecular dynamics. Our modelling team is on top of the latest developments and will readily implement any new type of digital experiment that becomes available. New tools and analysis techniques are continously developed in-house to strenghten and expand our pipeline and services.

What if the results of digital experiments do not match the actual laboratory results?

If this happens, the computer model needs to be updated for this specific project. The laboratory results will be verified, repeated and, when consistent, added to the model. Consequently, further modelling predictions will be more accurate. This is actually an indispensable part of the work and not only done when the results do not match. All wet lab data are fed into the digital test system for further model optimization.

How does EV Biotech assure the effectiveness of the model?

We provide a modelling report that shows the maximum efficiency that can be obtained with the strain. This report can be a go/no go moment if the desired target is not market competitive in its current state.

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3. Development / Strain Engineering

The core of our work is the development of microbial cell factories that produce your high-value compounds efficiently and sustainably, giving the highest yield while using as little resources as possible.

Benefits

In-house engineering and culturing of the microbial strains identified as most promising allows for short development times and direct feedback into the digital test system for further model optimization

Further development of MCF culture medium containing minimum carbon sources for optimal compound yield at the lowest price and environmental impact

Frequently Asked Questions

In what time frame can a strain be engineered and improved?

Our intake assessment includes a complexity rating, based on which we give a time frame. Roughly speaking, this process takes 6 to 24 months.

What happens in case the laboratory work takes too long?

If the laboratory work takes longer than estimated due to unforeseen problems in the development, we will report this to our partner and discuss with them how to proceed.

How is the microbial strain genetically designed?

The genetic design is created by using computational model predictions and digital data sets for identification of the enzymes that are required for the production of the target compound and its precursors. More information about the computational model predictions can be found under Modelling.

How is the microorganism selected for producing the compound of choice?

The computational model predicts the microorganism that gives the maximum theoretical yield in our available hosts. Our strain engineers then create this microorganism in the laboratory. If our partner has a preferred host, we will include this organism in our modelling and adjust our process if feasible.

Which microorganisms are used to produce a specific compound?

We use the most common industrial strains (E. coli, Bacillus strains, yeasts) for compound production. The metabolic pathways of these microbial strains are well-known and we have a variety of genetic tools at hand to modify them into compound-producing microorganisms. We closely follow the developments in the field and we are currently expanding our host base.

How does the computer modelling speed up the process of strain development in the laboratory?

The computational modelling predicts which microorganism, genetic modifications and carbon sources will give the highest compound yield and does so at a speed that is impossible to match by traditional trial-and-error lab experiments. We use these predictions as our starting point for strain development in the laboratory. The experimental data that we generate are fed back into the computer model to improve and correct the initial model and further optimize the MCF.

How does EV Biotech contribute to a bio-based economy?

We engineer microbial strains that grow on a minimum of carbon sources needed to produce the highest compound yield, resulting in minimal waste. Our virtual laboratory saves time, resources and energy, which makes our strain development process significantly more sustainable than the commonly used high-throughput, trial-and-error methods. Our processes are virtually carbon neutral, which sharply contrasts with the huge carbon footprint of chemical synthesis. We get our electricity from renewable sources and heat from waste streams of nearby industry.

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4. Upscaling & Support

We provide additional services to help optimizing the upscaling process by computational modelling, advice on any adjustments required for optimal strain production in industrial facilities, and strain maintenance

Benefits

Computational models on different scales help to choose the right culture conditions and setup that match the production facilities; including the possibility of adapting the MCF to the available resources

Continued MCF maintenance and strain improvement, even after implementation, to ensure that the compound production process is functioning optimally, also when circumstances change

Frequently Asked Questions

What kind of service do you provide when the MCF is ready? Is it included in the MCF development cost?

We deliver the MCF with customized growth protocol on lab scale. The next step is production on pilot scale. Depending on the conditions of the partnership, EV Biotech can organize this in collaboration with one of our preferred partners. For upscaling from pilot to full production we offer consultancy on a fee-for-service basis.

Do you produce the target compound? How big are your facilities?

No, EV biotech does not produce the target compounds in industrial quantities. The final production is outsourced to the industrial partner.

Do you perform the upscaling process?

We do not perform the process itself, but we can provide support service depending on the conditions of the partnership.

What if the yield of the MCF changes over time?

We offer fee-for-service support on problem analysis, including check of the genetic consistency of the MCF.

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