A Beacon for Biotech

Neil Clark ventures inside University of Nottingham’s new green chemicals hub

FILL, shoot, reload. During my PhD, a single pipette injection would take about five seconds – but this is a masterclass in monotony.

“Each one of those plates represents 96 small scale experiments, and this robot can probably do the work of  several PhD students in less time. More importantly, it frees the intellect of PhDs for creative problem solving.”

In the time it takes Alex Conradie to tell me this, eight pipette tips have sucked up a colourless liquid, filled eight wells of a 96-well plate, then been sent tumbling down a waste chute for replacement.

I’m trying to imagine how long those injections would have taken me – time that could have ultimately led to innovation and discovery.

“This is really going to be explosive in terms of how rapidly synthetic biology is exploited for commercial purposes,” Conradie continues.

Next, the full plate is grasped between a robotic finger and thumb, before being whisked off to an incubator in the glass housing that delimits the robot’s domain.

I pause to check the blurry photo I tried to take of this, but another experiment is already well underway. Fill, shoot, reload.

A beacon of excellence

I’m here at the University of Nottingham to see the facilities of, and hear the strategic vision of its Green Chemicals Beacon (GCB). My guide, Alex Conradie, is chair in sustainable chemical processing at the university, and is leading the initiative to “re-programme” how we think about chemicals manufacture.

The GCB is one of six beacons of excellence launched by Nottingham in June this year, with others including the Future Food, Rights Lab, Propulsion Futures, and Precision Imaging Beacons. Collectively they are guided by the UN’s 17 Sustainable Development Goals.

“We are looking at spearheading the transformation from a petrochemical energy-intensive economy to a more sustainable, or near carbon-neutral, bioeconomy,” Conradie tells me.

As one of three aims of the GCB, this focus plans to impact upon UN goals such as climate action and sustainable industrialisation. The other aims are to focus on carbon feedstocks derived from waste streams with minimal impact on the food value chain, and to gear research towards carbon-neutral processing with favourable life cycle analyses.

While this may sound a little idealistic, Conradie assures me that the GCB’s approach is firmly grounded in reality.

Industry-led, multidisciplinary approach

Rather than fund individual projects, Nottingham’s multi-million pound investment in the GCB is directed towards equipment, people and digital resources. This five-year project is intended to build the capability for a range of disciplines to work in unison, to accelerate the development cycle of products from carbon feedstocks.

Ultimately, the GCB is offering to “connect the dots” for collaborators, in order to realise commercial gains.

“The main aim is to have a completely integrated technology platform encompassing all of these disciplines – all the way from TRL [technology readiness level] one through to level five,” he says. “This covers the stages of development from process conceptualisation through to technology demonstration.”

“Engaging with industry, we want to progress a project all the way through these TRL levels, so that our involvement as an end-to-end solution provider culminates in continuous production of a compound at g/h scale.”

Conradie sees eight disciplines as having their own important part in the GBC, from identifying product opportunities using economic and environmental modelling, to manipulating host organisms using metabolic engineering, and enhancing intermediates through sustainable chemistry. “Therein lies the opportunity for chemical engineers in particular,” he says. “Linking it all together so that you have a continuous bioreactor feeding into the primary recovery unit and then into the purification unit operations at large laboratory scale. I think universities have been remiss in not making the most of their knowledge. Many innovative processes have been stopped in their tracks because of a lack of integration.”

A range of products

A process that the GCB will use to showcase its capability is the gasification of sustainable carbon feedstocks, followed by conversion of the CO₂ and H₂ to acetaldehyde.

This would involve feeding CO₂ and H₂ into a gas fermentor, with a biocatalyst host microorganism converting it to acetaldehyde, which is then recovered efficiently from the gas phase. Through chemo-catalysis, the platform chemical can then be converted into sustainable products such as 1-butanol, a drop-in fuel, or pyridine, a precursor to pharmaceuticals and agrochemicals.

“Such a project combines metabolic engineering, in creating the production host, with process engineering to recover the acetaldehyde; finally exploiting green chemistry to produce compounds of higher value. Thereby, the beacon’s integrated technology platform links the feedstock all the way to the product.”

This work will only take place, however, if an SME or large chemical company is interested.

“We really want to be solving industry’s problems, we don’t want to be solving our problems,” Conradie says. “We aim to engage with industry in meaningful ways. For example, two industrial biotech micro-companies have been welcomed into our labs to work hand-in-hand with us, providing a seamless transition of knowledge from academia to business.”

In terms of established corporates, he says that companies such as AB Sugar, Croda, FUJIFILM Diosynth Biotechnologies, LanzaTech and Sasol have been very supportive so far.

“Whilst we promote an open innovation environment, we are acutely mindful of the need to safeguard confidential knowledge. In building individual business relationships, trust and respect for each other’s intellectual property is paramount,” he adds.

With regards to funding, partnership awards such as the Industrial Strategy Challenge Fund will be sought. Conradie anticipates the beacon will break even towards the end of the five-year project, and be self-sustaining thereafter.

To minimise risk, he anticipates a diverse product portfolio. Initially, lower-value commodity chemicals will be targeted, as they can make a significant impact from a sustainability perspective, but higher-value chemicals are also being considered, such as cosmetic ingredients.

He says: “I don’t think there’s much of a limitation to what we could target. We’re opening up our capability for industry to engage with us, and the response so far has been very positive.”

As previously covered by The Chemical Engineer, Conradie sees flexibility as key to the future of chemicals production. He envisages multiproduct facilities, whereby organisms within bioreactors can be replaced and cultivated in a different manner – much like replacing a cartridge in an Atari games console – to manufacture a product as the market demands.

“It seems somewhat unusual that some of the processes developed in the 1960s and 1970s are still the processes in use today – it’s almost as if new innovative ideas need to come to the fore to start confining those to history,” he says.

Facilities

Alongside the visionary thinking, it is very apparent that the university is well equipped to achieve its aims – with more than its £1.1m liquid handling robot on show.

During my tour I am shown the highest concentration of anaerobic cabinets in the UK outside of the NHS, giving ample capability to work with host microorganisms such as acetogens, which are useful candidates when producing fermentative compounds.

We move on to the fermentation setup, equipped with advanced safety measures to allow laboratories containing flammable hydrogen and toxic carbon monoxide to exist side-by-side. Conradie tells me that this is a unique capability within academia, giving Nottingham an advantage over other universities globally when researching the use of C1 feedstocks.

Perhaps most impressive is the GSK Carbon Neutral Laboratory for Sustainable Chemistry: a £24m building with cutting-edge green credentials. It will become carbon-neutral within 25 years of operation, being capable of actively producing energy for the surrounding campus.

“In a green chemistry context, we’re really looking at reinventing how we think about chemical processes – this is the epitome of it,” Conradie says. “Buildings like these provide a sense of purpose. As an engineering scientist, you are drawn to thinking about designing processes to be in keeping with the ethos of the building.”

The labs inside are equipped with energy-saving measures: automatically closing fume hoods and turning lights off when unoccupied.

However, the most intriguing efficiencies in the building were around workflow optimisation – whereby mid-way through a lab, the clean floors give way to office carpet. These “invisible barriers” separate the desks of PhD students from their laboratory workstations, to save them time spent on navigating multiple doors and flights of stairs just to check a formula.

To me, this was a physical reflection of a university striving to remove barriers to stimulate innovation – and another thing to write below “science robot” on my PhD wish list.