A set of molecular switches enable researchers to push bacteria to produce higher amounts of desired chemicals and proteins. The idea is to limit cell growth while still maintaining the cells’ ability to produce chemicals.
By using the approach of decoupling growth, PhD Jenny Marie Landberg will make modified bacteria – so-called cell factories – produce larger amounts of specific bio-chemicals.
Today, the industry already uses bacterial cell factories to produce chemicals used in cosmetics, biofuels, plastic goods and as precursors for making both existing and new pharmaceutical drugs.
However, often the cell factories tend to only produce a very little amount of the chemical because they use a lot of the feed for basic metabolism.
“When you have cell growth there will always be glucose going into many cells, but if you stop the growth then you can direct the glucose into your product and enhance the cell factories to produce a larger amount of the desired chemical or protein,” says Jenny Marie Landberg, PhD at the Novo Nordisk Foundation Center for Biosustainability, DTU, and continues:
“The challenge is that when you inhibit growth, the cells often respond with a stress response where they just stop their metabolism. So, you want to have a mechanism that makes them continue being metabolically active.”
Growth decoupling
That mechanism is a switch that makes it possible to redirect the cell’s energy use from basic growth to making the desired chemical or protein. A method developed by former PhD at the Novo Nordisk Foundation Center for Biosustainability, DTU, Songyuan Li.
But while he focused on producing higher amounts of mevalonate acid and tyrosine, Jenny Marie Landberg focus mostly on L-serine that can be used not only to produce chemicals used in the cosmetic and pharmaceutical industry but also as a dietary supplement for people suffering from a non-alcoholic fatty liver disease.
According to a study published by the Mayo Clinic, the non-alcoholic fatty liver disease affects an estimated 80 million to 100 million Americans.
"One of the main issues is that the cell density quickly gets very high when you are trying to up-scale. But if you can push the cell growth to slow down, it gets easier and cheaper to produce chemicals in a sustainable way"
Jenny Marie Landberg, PhD student
“I am working on optimising serine production. One of the main issues is that the cell density quickly gets very high when you are trying to up-scale. But if you can push the cell growth to slow down, it gets easier and cheaper to produce chemicals in a sustainable way,” emphasises Jenny Marie Landberg.
Important to commercialise
If it is possible to increase the yield of serine per glucose, then the economic feasibility of the production increases as well. Basically, the nutrients should be used effectively for making the product to prevent it from being a major cost in the fermentation process.
While Jenny’s PhD project mostly focus on optimisation, the serine project, led by Professor Alex Toftgaard Nielsen, is already collaborating with the newly established pre-pilot plant at the Novo Nordisk Foundation Center for Biosustainability, DTU, to test if the work in the lab can be up-scaled.
“Personally, I find it particularly interesting to work on a project that can contribute to taking something from the lab and transfer it to the real life in higher scales via fermentation. Using cell factories is a great opportunity to reduce the dependence of oil and petroleum, so you cannot underestimate the importance of achieving to get real products on the market,” she says.
Jenny Marie Landberg is doing her PhD project as part of the Novo Nordisk Foundation Initiative’s PhD program.