The startups using light to scale biomanufacturing

The bioeconomy is associated with the production of tangible and weighty stuff. Yet some biobased startups are using a more ephemeral tool in their biomanufacturing processes: light. 

Developers of light-based technologies for biomanufacturing say their innovations could keep the costs of precision fermentation down by boosting yields and offering more control over what industrial microbes get up in the bioreactor. 

Lighting up precision fermentation 

One of the most versatile and exciting avenues to scaling biobased goods is precision fermentation, where microbes are used to grow large volumes of pretty much any target material. 

The end product of precision fermentation could be large volumes of cells from a tasty heritage cow breed (cultivated protein) or unique chemicals with no real analogue in nature (recombinant protein), made by inserting genes from various sources into the productive microbe.

For all its promise, the use of precision fermentation still faces scaling challenges. One of these is getting microbes to produce as much of the target substance in their bodies as possible. This is important because the more they can produce using the same amount of inputs, the lower the costs are for the end product. 

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Provectus Algae’s photosynthesising cells

Provectus Algae tackles the problem of cell factory productivity using a combination of LED lighting and photosynthetic algal species.  

One of the services offered by the company is a bioprospecting platform that discovers photosynthesising microalgae which are also capable of producing particular chemicals that are useful in industry. 

Finding algae that fit these two criteria is no easy task given that 99% of algae cannot grow in natural sunlight. Many species developed out at sea rather than on land where sunlight cannot reach at the same intensity. 

The company now holds a unique library of species all ready to be optimised for producing high-value chemicals in their bodies at an industrial scale under light.

In Provectus’ biomanufacturing process, light is not just a passive element consumed by the cells in photosynthetic processes as they grow. Provectus has developed bioreactors that are complete with LED lights that remote users can adjust in their spectrum, intensity, and flickering frequency. 

By changing the type of light, the company can manipulate the algae’s genes, switching them on and off to determine the kind of chemical they are producing in their bodies. 

Prolific Machines controls cell growth with light 

Another obstacle to scaling precision fermented biomanufacturing is the complexity of living processes and the difficulty of controlling this in industrial contexts. 

Growth is one biological process that poses problems for producers if nature is allowed to run its course. Precision fermenters may perfect their microbial manufacturing line only to find that two years on, random mutations have impacted the productivity of the microbial population or the quality of the product that it makes. 

This problem of genetic mutation and declining product quality is most problematic for precision fermenters that use continuous microbial fermentation as a method of production. In a continuous reactor, the media – the liquid where the bacteria is growing – is constantly being replenished. This differs from the batch system, where each production batch is closed and any contaminant has limited opportunities to ruin the whole stock. 

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Producers want predictable, consistent biobased commodities while nature is often happy to indulge in a bit of chaos. How can biomanufacturers exert better control over microbial cultivation? Prolific Machines believes that the targeted use of light could become the most economical solution to this scaling problem.  

Light can have a rapid impact on cellular processes such as gene expression, receptor activation, and enzyme activity – all relevant in growing target chemicals inside their bodies. 

Prolific has managed to develop microbes that respond to light changes by altering the receptors inside them. Usually in nature, the cellular behaviours of microbes would change instead in response to external chemicals. Prolific’s custom-tweaked industrial microbes are instead designed to alter their behaviours when exposed to light of different colours, intensity, and patterns. 

In Prolific’s system, biomanufacturers can use different kinds of light to determine what the microbes produce, where, and in what arrangement. This gives greater control to the producer over what the microbes are doing in the bioreactors, allowing for a much more fine-tuned process of making chemicals and biomaterials. 

For example, shining a targeted light into a particular group of cells in a batch could pick out these cells while leaving the rest alone, allowing for small-scale alterations. This can be useful for food tech entrepreneurs trying to achieve proteins with complex and varied textures.  

Brevel replaces gene editing with light

Light-based biomanufacturing is an emerging technology but there is a growing list of precision fermentation companies that are fine-tuning it. 

One of them is Brevel, an Israeli company founded by three brothers: Yonatan, Ido, and Matan Golan. Brevel grows and extracts protein from photosynthesising microalgae to create a neutral-flavour protein powder ready for processing into consumer-ready animal meat substitutes. In 2023, the company operated a 500-litre bioreactor, targeting a 900,000-litre capacity by 2025.

Brevel aruges way that it uses light in microbial cultivation could make its products much more cost-competitive relative to cheap farmed dairy and meat commodities. Like Prolific, Brevel aims for just the right interplay between light and fermentation in a bid to perfectly optimise its biomanufacturing process. The fermentation takes place in a mostly dark environment, broken up by the targeted use of LED lighting. 

Usually, when precision fermenters want their microbes to become more efficient chemical producers, they rely largely on genetic tools. However, Brevel says that their light technologies are powerful enough to replace genetic modification as a means of increasing protein yields from the microalgae. This opens the door not only to larger product volumes but could also remove the regulatory barrier in the way of marketing genetically modified foods in certain markets. 

The main advantage of being able to use light patterns as a means of controlling the cell production process is that it promises to be much more precise than the methods that producers currently use. 

Right now, it is common for precision fermenting companies to place chemicals in their bioreactors to try and direct the cell production process. Yet the interactive effects between these chemical inputs and the living cells are unpredictable.

This unpredictability can end up resulting in bloated production costs and, ultimately, a product that does not scale. Yet according to Brevel, the use of light can stimulate product growth and triple profitability from the same batch of microalgae simply by encouraging more yield production. 

In 2022, it partnered with vegan food maker VGarden to develop a plant-based cheese that launched globally after obtaining regulatory approval for novel foods. Brevel itself will launch its own products beginning in 2025. 

An economic solution for food tech 

LED lighting is relatively inexpensive compared to other potential instruments of biotechnological control, such as chemicals and gene editing. 

Using a ‘language of light’ to control biomanufacturing could therefore become a cheaper and more intuitive way of working for bioproducers, who often have to rely on trial and error to perfect and maintain their industrial processes. 

The cost savings offered by light-based forms of microbial manipulation would have the greatest impacts in the field of food tech compared to fermented cosmetics and pharmaceuticals. 

One of the biggest expenses involved in precision fermentation is the nutrient-rich liquid media that forms the backbone of the process. This is the substance that sustains the industrial microbes inside industrial bioreactors where they grow and produce chemical products. 

Producers that manufacture for the pharma and beauty sectors can often make back the costs by selling at a high price point. Consumers do not mind paying high prices for niche beauty and health substances they buy in low volumes. 

Edible proteins, however, are a different consumer proposition altogether, being an everyday supermarket item that has to compete with much cheaper dairy and protein made from industrially reared animals. The costs of precision fermented meat are still much higher than ordinary proteins, putting pressure on the industry to find innovations that can bring it down to competitive levels. 

Light-based microbial cultivation may be in its early stages but the number of startups using LEDs in biomanufacturing are on the rise. While it might seem like an esoteric route to biomanufacturing, light is an abundant, cheap, and safe resource, meaning that it could contribute to achieving a much more streamlined biomanufacturing process.

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