*EASTBIO* A molecular toolbox to commercialise cyanobacteria: synthetic genetic sensor-regulator circuits for increased yields of phycobiliproteins

Cyanobacteria are increasingly recognized as valuable platforms for industrial biotechnology. Good genetic tools are available for many species, as well as complete genome sequences and metabolic models. They are metabolically diverse, and encode a large number of P450 cytochromes that are valuable for metabolic engineering. Importantly, they are an established bioplatform for production of phycobiliproteins, including the high value pigment C-phycocyanin (C-PC). C-PC is an important component of the pharmaceutical, nutrition and cosmetic industries with a market value of £35 million that is expected to grow ten-fold by 2018. Market values of C-PC can reach up to £52/g (1). A major challenge for cyanobacterial IB is that culture stability and PBR conditions are difficult to maintain, which often leads to large fluctuations in biomass production and downstream yields. On the other hand, rapid market growth has led to demand outstripping supply on C-PC. Thus, there is a strong commercial need to develop robust, high accumulating C-PC strains for reliable production.

Our goal is to use a novel synthetic biology-based approach to develop robust strains of cyanobacteria that produce significantly increased yields of C-PC, in collaboration with our industry partner, Scottish Bioenergy which designs, installs and operates microalgal photobioreactor systems for biochemical production. The productivity of cyanobacterial cultures is restricted by limitations in control of growth and metabolism, often leading to large fluctuations during the biomass production process and downstream yields. We will design dynamic cellular gene control circuits that are able to sense and respond to the surrounding environment, and then co-ordinate cellular metabolism with C-PC production (2,3). This is a game-changing approach that goes beyond the simple use of genes driven by powerful promoters for bioproduction, with little consideration of the physiological consequences. Proof of the commercial viability of our concept will be demonstrated by modifying the output of the gene control circuit to regulate the production of C-PC, and then testing new strains in industrially relevant (up to 1,000 l) photobioreactor conditions. The modular approach of our system will allow future scalable circuit designs to direct metabolism in response to the input level of combinations of different environmental signals for optimising the production of other high value products.

The project will provide the student a comprehensive training of advanced molecular cloning and genetic tools, innovative synthetic biology techniques and industrial biotechnology skills. The research thus gives the student an inter-disciplinary research experience and cutting edge technologies exposure to prepare well for his/her future career. The student will also benefit from the opportunity to work collaboratively with our industrial partners in biotechnology.