December 2015

The University of Edinburgh, Cambridge University and Scottish Bioenergy win Phyconet Grant in Synthetic Biology. Many thanks to Phyconet and BBSRC and all our Partners.

Phyconet Award Notice

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

Alistair McCormick (University of Edinburgh)

Cyanobacteria are an established bioplatform for production of natural pigments, such as the phycobiliprotein C-phycocyanin (C-PC). Growing global interest has attracted considerable investment to bring cyanobacterial culturing technologies to commercial scale. However, investment in synthetic biology-based approaches to develop robust strains is still lacking. The market for cyanobacterial-based pigments is projected to reach £1 billion by 2019, at a CAGR of around 3.5% from 2014 (www.marketwatch.com). The FDA approved C-PC as a food colourant in 2013 and it is globally recognized as safe (GRAS) in nutritional supplements, cosmetics and pharmaceuticals. In the nutraceutical market C-PC is used as an anti-oxidant, while the use of C-PC as a natural blue food colourant (e.g. blue M&Ms) has experienced significant growth in the past five years (as confirmed by our industrial partner). Cyanobacterial pigments, such as C-PC, are also promising candidates for drug discovery, with applications in hepatic repair, cardiovascular disease, immune support, neurodegenerative diseases and next generation antibiotics. Exploitation of C-PC by the pharmaceutical, nutrition and cosmetic industries has given this biochemical a high market value; the £35 million market for it is expected to grow ten-fold by 2018, and demand has outstripped supply for C-PC.

Scottish Bioenergy designs, installs and operates microalgal photobioreactor systems for biochemical production and is seeking new approaches to meet this market demand. 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. 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. 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.