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Development of tools to increase product yields in cyanobacteria using a synthetic biology approach

Periodic Reporting for period 1 - Cynthetica (Development of tools to increase product yields in cyanobacteria using a synthetic biology approach)

Reporting period: 2017-06-01 to 2019-05-31

What if we could find a renewable and sustainable source of fuels, pharmaceuticals and functional foods? Cyanobacteria are fast-growing photosynthetic blue-green bacteria. This means they strip carbon dioxide from the atmosphere and use sunlight to produce oxygen and energy. Their sustainable nature have put them at the forefront of the green revolution that aims to deal with rising global challenges such as climate change and fossil fuel depletion. However, despite the enormous potential, the full exploitation of cyanobacteria is still in an early development stage. Therefore, to make Cyanobacteria competitive with current established microbial cell factories, we need to improve them. The objective of Cynthetica is to utilise Synthetic Biology to increase product yields and make green cell factories more competitive.
Cynthetica aimed to apply synthetic biology principles to improve product yields in cyanobacteria. All work was performed in two cyanobacteria: a well-studied model organism and in a novel fast-growing cyanobacterium of biotechnological relevance. This organism can grow at similar speeds as certain yeast strains, but solely with carbon dioxide and sunlight unlike yeast which requires sugar to grow.
I focused on two tools: the “anchor tool” and “capsule tool”. With the anchor tool I focused on improving membrane protein expression in cyanobacteria. Membrane proteins are very difficult to express, however, they are of great industrial importance. This is particularly true for proteins involved in the production of high value compounds, such as cytochrome P450s.
As part of the capsule tool, Cynthetica aimed to improve the output of a biosynthetic pathway. By generating dedicated locations for product synthesis, we can optimise product flows, thus making the process more efficient and less toxic to the cell. Interestingly, Cynthetica has found that certain fast-growing cyanobacteria are particularly well suited for this approach and are comparable to current non-photosynthetic hosts.
Over the course of the project we have followed the building principles of synthetic biology, therefore, the tools created are user-friendly and ready to be shared with other researchers and industrial users. Additionally, the project was disseminated to a wide range of audiences. I have presented this work at 5 international scientific meetings and I have been a co-author on, so far, 2 peer-reviewed open access publications. I am now in the process of building my own research group based on this project. More results from Cynthetica remain to be published and will be made available to the scientific community through open-access publications.
Since the start of this project there has been a marked increase in societal awareness of the future risks presented by global warming and climate change (see the “Greta Thunberg Effect” and “Fridays for Future”). Therefore, it is crucial that we invest in sustainable, green, technologies that can transform the current industrial infrastructure. In the light of this, cyanobacteria are of great interest and need further development efforts. The work developed in Cynthetica will aid in improving these green hosts and pushing them into the biotechnological spotlight. This is important to establish a role for green biotechnology in the future European biotechnology landscape and will contribute to novel, sustainable, solutions to tackle our upcoming socioeconomic challenges.