Mario Toubes-Rodrigo, global applications leader, H.E.L Group shares how high pressure bioreactors can transform fermentation for a sustainable tomorrow.
FOTOGRIN Shutterstock
The history of using bioreactors for fermentation processes stretches back over 10,000 years, when pottery vessels were used to ferment a mixture of rice, honey, and fruit in China, but it was not until the 1950s that we started to see their use in pharma and biotech. Nowadays, bioprocessing plays a critical role in these industries, with emerging trends such as using sustainable feedstocks and waste byproducts to manufacture valuable and renewable products offering a novel approach to solving global challenges in sustainability.
Developing the optimal bioprocess
Optimising bioprocesses requires a multidimensional approach; balancing yield, efficiency, and costs. Increasing the product titre reduces the need for expensive recovery processes, while increasing the volumetric productivity is intrinsically linked to higher yields, but both approaches have high set-up costs.
The critical question we need to answer is: “how can we achieve cost efficient high yield fermentation?”.
Unsurprisingly, there is no straightforward solution, and instead, we need to evaluate all moving parts in the process. A good starting point is choosing the most appropriate microbe – one that is capable of producing large amounts of the molecule of interest, while being easy to cultivate.
Each microbe has its optimal conditions for growth, requiring a water- and feedstock-rich environment with a constant temperature and pH. Given the exothermic nature of fermentation, bioreactors must be equipped with effective thermal management controls to keep within the optimum growth parameters. Alternatively, microorganisms can be selected genetically engineered to tolerate greater fluctuations in temperature, increasing product yield.
But even the right microbial strain can only go so far. Researchers must evaluate other factors, such as pressure, volumetric productivity, and appropriate sustainable feedstocks to optimise fermentation processes.
Waste products as a sustainable feedstock
Among potential sustainable feedstocks, carbon dioxide (CO2) stands out as a good option. It is cheap, is produced as a byproduct of numerous manufacturing processes, and is a major contributor to global warming. Reducing the production of this gas and removing it from the atmosphere has become a critical goal for governments and industry alike, with decarbonisation strategies emerging as a priority. Applications such as carbon capture and utilisation (CCU), in which CO2 is removed from industrial processes or the atmosphere, reduce environmental footprints and will be a key part of the circular economy.
High-pressure reactions to enhance gas bioavailability
An additional factor that limits the efficiency of fermentation is the accessibility of feedstock: gases are notoriously hard to dissolve in water, and CO2 is no exception.
Henry’s Law states that the amount of a given gas that dissolves in a given volume of liquid is directly proportional to the partial pressure of the gas in equilibrium with the liquid. In practical terms, increased pressure favours the dissolution of gases in fluids, in this case, water or cultivation medium, thus increasing the volume of gas available for organisms.
Microbial cells (including bacteria, archaea, and fungi) are well equipped to withstand these pressurised conditions due to their robust cell walls and small surface areas, and are capable of maintaining their structural integrity and functional capabilities throughout the reaction, meaning that an increase in pressure has no detrimental impact on cell growth, only improves the specific productivity and carbon conversion, increasing both the molar yield and efficiency.
Increasing the pressure of these systems might seem to incur higher production costs at first glance; the bioreactors need to be compatible with extra specifications including the use of metal reactors (e.g. stainless steel) able to withstand the harsh conditions, and reinforced connections, avoiding potential leaks. However, the benefits quickly outweigh the initial investment. The use of robust instrumentation with proper materials will ensure the longevity of systems and the safety of the bioprocess, reducing the need for maintenance. Optimising gas bioavailability under these conditions significantly boosts yield and productivity, making high-pressure fermentation a cost-effective and sustainable solution.
Current trends in High-Pressure Bioreactors
Although high-pressure vessels for chemical processes have been around for some time, their application to biological processes is much more recent, and their advantages are still being demonstrated. Robust materials and engineering designs ensure that bioreactors can maintain high-pressures for extended periods of time, as well as preventing contamination through effective seals and decontamination approaches such as autoclaving and sterilisation. Modern systems equipped with precise control mechanisms allow real-time monitoring of the process and the use of automation reduces the manual effort required to maintain optimal conditions while decreasing potential for human error. These innovations are opening doors for applications beyond traditional fermentations.
High-pressure bioprocessing can be used to upcycle waste byproducts into valuable chemicals, supporting the circular economy and reducing environmental impact. A recent study demonstrated the use of genetically modified organisms, Cupriavidus necator to produce isopropanol from CO2 in a pressurised bioreactor. Isopropanol is a common solvent used in the manufacturing of cellulose, plastics, and resins, as well as having applications as a disinfectant and cleaning agent. In this example, the fine control and sensitivity of the bioreactor allowed for the introduction of H2 gas, without reaching dangerous levels that lead to explosion, or inhibiting the enzymes of the microorganism, allowing for the effective fermentation of gases with a yield equivalent to that obtained using fructose. This approach offers a cost-effective method of production that avoids using resources valuable for human consumption.
One industry in which this technology holds huge potential is in the manufacturing of sustainable aviation fuels (SAF). The high-pressure fermentation of CO2, CO, and H2 using anaerobic microorganisms such as acetogens to produce alcohols offers a sustainable method of decarbonising the aviation industry using the existing aircraft and infrastructure.
Driving the future of bioprocessing through high pressure
High pressure bioreactors are proving to be a transformative innovation in fermentation technology. Improving gas bioavailability, improve the yield and productivity of bioprocesses, supporting both economic and environmental goals. As industries and governments push for sustainable manufacturing, the role of high-pressure systems will only become more prevalent, driving advancements in fields such as biofuels, pharmaceuticals, and more. With the right investment and cross-industry collaborations, high-pressure fermentation has the potential to redefine how we approach bioprocessing and contribute to a more sustainable future.