Precision fermented proteins could support a more sustainable food system. Yet scaling the technology remains difficult and costs are still too high to be competitive for the mass market.
Now, precision fermentation startups like Cauldron and Pow.Bio believe they have a solution: continuous processing. We look at how it differs from prevailing methods of production and how it could bring down the consumer prices of biomanufactured goods.
Continuous versus batch processing
Precision fermentation is a way of ‘brewing’ materials from scratch inside custom microorganisms.
Used for decades in biopharma, precision fermentation capacity for products in food, nutraceuticals, and industrial chemicals is growing. Now, harvesting exact beef replicas or as-yet undiscovered proteins from modified bacteria is no longer the far-off vision it was even twenty years ago.
At the heart of all precision fermentation systems are microbes. Whatever species are used, these industrial microorganisms are designed to produce a particular protein or chemical inside their bodies.
The basic biotechnology mimics the way we have been brewing beer or making cheese for millennia – except in precision fermentation, microbes have not been gradually selected through trial and error for tasty secretions. Instead, they are genetically engineered to produce a specific material.
These functional microbes become living, miniature ‘factories’ once placed inside temperature-controlled soups that contain all the nutrients they need to stay alive and produce the target material. Once they have matured, the chemicals they have been engineered to produce are harvested from their bodies.
There are two main methods for cultivating and harvesting from microbes: batch and continuous processing. Batch is the most common method today in precision fermentation.
Under batch processing, the microbes are grown in the bioreactor soup and then removed from it for harvest once they are mature. After they are removed the bioreactor they were growing inside is cleaned out. A fresh colony of microbes is grown inside it. The new microbes grow and the process repeats.
Continuous fermentation is relatively self-explanatory: here, producers continuously harvest the chemical from the microbes without ever emptying the bioreactor. This means that unlike the batch process, the number of productive microbes inside the bioreactor stays relatively constant.
To achieve this, the producer continually adds new feedstock (whatever the microbes are fed on: sugars, other nutrients, gases) as they harvest chemicals from the microbes.
Fewer stoppages mean lower costs
The difference between continuous and batch precision fermentation may appear subtle but their impact on operating and capital costs can be significant.
Comparison experiments have shown that continuous processing can reduce capital expenditure by three to tenfold. This is a significant advantage, especially at a time when sustainable biotech investments generally have been slowing and investors have become more selective about projects in the space.
The reason continuous fermentation is a better cost proposition is that there are no stoppages like there are in the batch process. In batch production, cleaning out the bioreactor and waiting for the brand new microbial culture to mature again means there are regular intervals where productivity falls to zero. Because under continuous processing, the microbes are productive for longer, using it means it should take less time for producers to break even on capital costs.
Boil and bubble
Australian precision fermentation startup Cauldron has been pushing continuous fermentation to the forefront of industry awareness. Its technology, which it calls the ‘future of biomanufacturing’, could make fermented chemicals and materials competitive with non-fermented goods for the first time, according to the company.
Right now, the high capital costs of precision fermentation mean that products made using the technology only make financial sense in high-value, low volume markets, such as biopharmaceuticals or specialist enzymes.
What Cauldron is trying to do is to use continuous processing to bring down the costs of precision fermentation until it is cheap enough to produce low-value consumer goods. These include products made from animals or petrochemicals today but could instead be made in labs using just biological materials. One target product is casein: the milk protein that gives cheese its distinctive texture and creaminess.
Keeping biology in check
Working with living organisms, particularly microorganisms, in industrial settings is always a hard task. Compared to chemicals and machines, random mutations and unintended side-effects are always a risk when using near-invisible biological entities that move, metabolise, and evolve.
Despite its costs, batch processing has one key advantage: removing and cleaning out the bioreactor between harvests decreases the risks that unwanted microorganisms will taint the mix. While batch processing may not make sense from a commercial perspective, it can make for a higher quality and more consistent end product.
Cauldron’s solution to prevent contamination in continuous processing has been to devise bioreactor media – microbe food – that is fine-tuned to the nutritional needs of just the functional species being used in the process.
Another advantage of batch processing, with its regular bioreactor emptying and sterilisation, is that it prevents genetic drift: gradual, random changes in the genetic make-up of the microbe population. As microorganisms proliferate, mutations in their genetic code could quickly take over, working against product consistency.
Cauldron has also come up with workarounds for genetic drift, with a pack of proprietary operating protocols designed to promote genetic stability.
Pow.Bio’s dual chamber process
Continuous processing is all about raising the productivity of each microbe in the bioreactor. Productivity increases are key to cutting costs in precision fermentation, as it allows the producer to effectively squeeze more marketable products out of the same starting capital and operating costs.
Pow.Bio, founded in 2019, is another firm selling a continuous processing platform that it says cuts costs drastically. The company claims that its technology can reduce unit costs of fermented products by between 40 to 70% compared to batch processed goods thanks to a five to ten-fold increase in productivity.
The startup has slightly different solutions to Cauldron when it comes to solving the key problems of microbial contamination and genetic drift: a separate bioreactor chamber for microbial growth and for microbial chemical production.
Microbes grow only in the designated growth chamber, which is separate from the production chamber. Once the microbes enter the production chamber, they stop growing – they simply produce the target chemical. The trick is that if the functional microbes cannot grow, neither can any unwanted microbes that have contaminated the soup.
Gas into goods
French startup UniBio is a continuous fermentation startup with a difference. Instead of feeding its microbes sugars, it uses natural methane.
It is possible to rear microbes on gas because methane and biological materials have one major element in common: carbon. Animals are full of carbon because they eat material containing the element, turning the inert element into living cells through complex metabolic processes.
Usually, precision fermenters use functional organisms that draw carbon from sugars, commonly taken from plant matter. UniBIo’s method is different because it exploits a unique class of organisms known as methylotrophs.
Methylotroph feeding requirements are much more stripped down than most living things, needing just single carbon compounds – something that natural gas can provide all on its own. These creatures can do away with traditional sources of food altogether consisting of any biological matter.
UniBio feeds its proprietary methylotrophs with pure oxygen, methane gas, and minerals such as nitrogen. This set-up is continuous so the methylotrophs are constantly feeding on gas and forming new protein compounds from the raw ingredients inside their substrate soup.
Used in combination with continuous processing, UniBio’s unique system could drastically lower the costs of precision fermentation. Compared to sugars drawn from crops or other biomass, methane is an incredibly cheap raw material. It is also a potent greenhouse gas, opening the way for a circular fermentation process that draws on emissions from industrial plants and agriculture.
Novel proteins in global competition
Our global food systems are coming under pressure with land, water, and stable growing climates becoming scarcer. Industrial livestock is also a major contributor to climate change and habitat loss. Precision fermentation is seen as an important technology in relieving some of these issues while feeding growing populations.
So far, efforts to develop and scale precision fermented protein have been playing out in the private tech sector. Yet it could soon get major policy attention. In 2021, China made it clear that it wants to develop and scale meatless, slaughter-free alternatives to pork, beef, and chicken.
Fermented proteins could now shape up to become the latest arena of tech competition between the US and China. Last year, China’s National Health Commission accepted 22 novel food ingredients, including fermented-derived human milk oligosaccharides. The sector there is only set to grow.
In recent years, Western investment into the sector has been volatile. A consumer health and wellness boom over the pandemic led to a historic expansion of the precision fermentation sector that quickly hit an inflationary wall after 2022.
If the case of solar panels and EVs are anything to go by, China’s entry into the world of novel protein could soon spur policies in the West that are favourable to scaling the sector. Precision fermentation would be among the solutions first in line to benefit, with continuous processing platforms promising a viable path to cost reduction.