Team:DTU-Denmark/Implementation

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Proposed implementation

Our project has been aimed at improving manufacturing in the biotech industry. Therefore, coming up with a solution that can actually be implemented at scale has been one of our highest priorities when designing our project.

In order to understand the road to implementation it is important to be aware of where in the production chain we fit in. That is in the actual fermentation of bioproducts. Specifically the production of proteins, such as enzymes and secondary metabolites in Aspergillus niger cell factories. This organism was chosen because it is one of the most widely used filamentous fungi. This includes the impressive repertoire of several commercial enzymes and being the world's largest producer of citric acid. Companies that use A. niger include DSM (The Netherlands), Zymergen (USA), Novozymes A/S (Denmark) COFCO (China), RZBC Group, (China), etc. (Arnau et al., 2020 ; Cairns et al., 2019 ; Meyer et al., 2016). This also gave us the opportunity to get feedback and advice from the industry which we suggest you can check out in our integrated human practices section integrated human practices section.

A particular challenge for improving production is that most strains have already been highly optimized for widely different purposes. Some production strains in the industry have been optimized through decades of pathway engineering and strain optimization enhancing them for citric acid or enzyme production. Strain optimization is a long, expensive and labour intensive process and changing host strain is therefore costly and risky.

Our solution has been designed in a way which enables the integration into already established production strains of A. niger as well as new ones. In addition it won’t require any large investments into new equipment or personnel and will therefore be attractive to implement. We have achieved this by designing a parts collection that can change the morphology of A. niger. We therefore see our solution being implemented by any company having an established production in A. niger or trying to set up a production by following these easy steps:

1. Choose an established or new A. niger stain ready for production


2. Determine what morphology that is desired for that production


3. Choose the genes that can be knockout to archive that morphology from our library


4. Knockout these genes using our parts library


5. Reintroduce or begin large scale fermenetation production using the newly modified strain

Hereby any company in the biotech industry should be able to achieve the desired morphology. Furthermore, to validate that the desired modification is working in proprietary industrial strains our image analysing tool Morphologizer can be used. We therefore highly suggest that you check out our part collectionand the Morphologizer.Finally in order to test out our implementation route, we took our project findings to Novozymes (the world's largest manufacturer of enzymes). They were very interested and to us that indicated that this would be the best way to implement our solution to the real world beyond iGEM.

Our hope is that by making it more straightforward to control morphology the biotech industry can increase its output. Hereby we hope that processes that were otherwise produced in the petrochemical industry can be replaced by sustainable cheap production in A. niger cell factories.