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Artificial colourings have fallen out of favour with consumers and created high demand for natural alternatives. A collaboration between Edinburgh researchers and biotech firm ScotBio has found a scalable solution in algae.

From Smarties and soft drinks to cosmetics and textiles, blue colouring is in so many of the products around us, but artificial colourings have become unpopular with consumers who are increasingly conscious about what goes into the things they buy. This change in buyer behaviour has generated unprecedented demand for natural colourings that can perform well across a range of applications.

In 2012 a fledgling Scottish biotech company partnered with a group of University of Edinburgh scientists to explore how a natural blue colouring can be cultivated and extracted from blue-green algae. The collaboration has since gone on to make pioneering breakthroughs, enable significant company growth and sustain a thriving partnership with the University that continues to expand into new areas.

True Blue

Artificial blue colouring of the kind you might find in sports drinks and children’s sweets is a petrochemical by-product, which in today’s health-conscious culture is a cause of significant consumer concern. The problem is that most of the blues we see in nature are not really blue at all, but rather elaborate optical illusions. This makes a natural true blue from which pigment can be extracted exceptionally rare.

One source of natural blue colouring is phycocyanin, a pigment-protein naturally produced in blue-green algae otherwise known as cyanobacteria. The main method of phycocyanin cultivation involves cyanobacteria being grown in vast, shallow outdoor ponds to enable photosynthesis, but this process comes with all the common problems that are inherent to an agricultural manufacturing method, namely competition for space and freshwater; exposure to contamination risks; reliance on unpredictable weather systems; and security issues. In short, the established system for cultivating phycocyanin is far from the reliable, efficient and predictable process required to cope with an ever-increasing demand for natural blue colourants.

A colourful collaboration

In 2012, University of Edinburgh molecular biologist Dr Andrew Free was investigating how communities of microbes could be used to do important environmentally-related tasks when he was put in touch with David Van Alstyne, Founder of Scottish Bioenergy, an early incarnation of what would later become biotech company ScotBio. Van Alstyne wanted to explore the potential uses of phycocyanin and Free, who had not engaged with industry before, was interested in the possibilities this project held.

The pair wasted no time in recruiting PhD student Rocky Kindt, who was put to work analysing samples taken from photobioreactors - fermentation vats fitted with specialised lights - in which algae biomass was being grown under a variety of conditions. Dr Free explains

We wanted to understand some of the microorganisms living in those reactors. To see how those organisms interacted with the cyanobacteria to either help its production of the pigments that the company wanted to produce, or in some cases were perhaps hindering its growth and production of the pigments.

This initial work was facilitated by the contribution of materials and equipment from the lab of Newcastle University’s Dr Gary Caldwell, another ScotBio collaborator.

Kindt was enthusiastic about the work he and Free were doing with ScotBio, and the interplay between academic research and industrial need was a big part of that appeal.

I was very much attracted by the exciting routes toward having real-world impact. It was interesting to work from the company’s angle too, in terms of trying to understand these discoveries and how they could be realised in a commercial application.

Kindt’s passion and expertise made him an appealing hire prospect for ScotBio, and upon completion of his PhD he was offered a job with the company. He now heads ScotBio’s R&D arm and is Chief Technology Officer.

Reflecting on the partnership’s successes to date, Kindt credits Free and the early work conducted in his lab with setting the scene for ScotBio becoming the company it is today. Kindt says

It was through Andrew Free’s support and his laboratory that we were first able to understand how to handle this material and the complex processing chain towards getting a purified blue material out at the other end. The access to expertise, facilities and resources at the beginning made possible the fundamental things that led to ScotBio growing, getting funding and being where it is today.

By 2015 the research team had developed a patented, containerised system for cultivating phycocyanin, the natural blue colouring. While the traditional system cultivates algae in exposed, open ponds and relies on sunlight to photosynthesise the cyanobacteria, the team’s closed, controlled containers were fitted with specialised lights to replicate the sun’s rays. This provided a level of traceability, security and reliability of supply that had never been possible before, and would be highly desirable for brands making the move to using natural colouring in their products.

ScotBio was keen to scale up production so that it could supply its natural blue colourant to a ready and waiting commercial market. At this stage Dr Alistair McCormick, then a new Chancellor’s Fellow at the University of Edinburgh, was introduced to the partnership by Edinburgh Innovations, the University’s commercialisation service, to maximise the yield of phycocyanin and bring them closer to commercialising their discovery.

Blue Ribbon

McCormick’s first move was to secure a proof-of-concept funding grant from the BBSRC NIBB Phyconet, so that he could explore new ways of purifying phycocyanin using a highly specialised and targeted filtration method called chromatography. This approach proved extremely effective, yielding a hitherto unachievable level of purity, and making the partnership’s phycocyanin suitable for the pharmaceutical, nutraceutical and therapeutics markets.

The commercial returns on purity are significant, according to McCormick. Food grade level phycocyanin is available for quite a low price, but one gram of analytical-grade phycocyanin is worth around £100,000.

In addition to this breakthrough, which significantly enhanced the company’s commercial prospects, McCormick was able to put together a molecular toolbox for engineering cyanobacteria that is now available to buy, meaning the potential applications for microalgae can now be investigated by academics across the world.

In 2019, the partnership won a prestigious Scottish Life Sciences Award for their pioneering collaboration on natural blue colourants. They were awarded the Innovative Collaboration prize for their development of new molecular biology and extraction techniques to boost the yield and purity of ScotBio’s phycocyanin product.

The partnership’s award-winning innovation puts the company in a strong position to lead in the rapidly growing market for natural food and drink colourants, and to become a major player in the pharmaceutical market. Kindt says

It has allowed a small company to really punch above its weight in terms of the types of challenges it could dare to try and overcome. We’re able to distinguish ourselves from our competitors in offering something that is scalable, predictable, and can be deployed anywhere in the world.

New horizons

The successful partnership between the University of Edinburgh and ScotBio continues, with new projects and plans for further company growth underway. ScotBio is in the process of expanding its manufacturing facilities, and it has been awarded funds from Medical Research Scotland and the Industrial Biotechnology Innovation Centre (IBioIC) for a new collaboration involving McCormick and Dr Richard Sloan from the Infection Medicine centre within the Edinburgh Medical School. The project will investigate the antiviral and antimicrobial bioactives that are naturally present in cyanobacteria, with an aim of discovering new therapeutic treatments for viral diseases.

A collaboration between what began as a very small biotech company and three researchers who had never engaged with industry before has been an overwhelmingly positive experience for all involved, and one that has made significant commercial and research impacts. The tremendous success of their partnership is proof of the potential that is waiting to be unlocked when academic expertise and industrial aims are aligned.

Header image: vienetta14/

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