Could single-celled fungi help fermentation move beyond farmland?  

Fermentation is increasingly presented as one of the most promising ways to produce the food ingredients, materials and chemicals of the future, yet many of these processes still begin with a familiar resource: farmland. 

Today, many industrial microbes are fed with sugars derived from crops such as maize, sugarcane or beet. These sugars provide the carbon and energy that microbes need to grow and produce valuable compounds, including proteins, fats, colours, flavours, nutrients and bio-based materials. 

As fermentation expands, this creates an important question for the future of sustainable production. If microbes are expected to make more of the ingredients and materials society needs, the resources used to feed them will matter just as much as the products they create. 

A new study led by Professor Rodrigo Ledesma-Amaro from the Bezos Centre for Sustainable Protein and the Microbial Food Hub at Imperial College London points to a different possibility. Instead of relying primarily on crop-based sugars, future fermentation systems could use carbon-derived compounds made from CO₂ and electricity. 

Published in Nature Synthesis, the research shows that the industrial yeast Yarrowia lipolytica can be evolved and engineered to grow on formate, a simple one-carbon compound that can be produced from captured carbon and renewable power. 

The work remains at an early stage, although its implications are significant. It suggests a future in which fermentation could place less pressure on farmland while continuing to produce useful ingredients, nutrients, colours, materials and chemicals. 

Moving beyond crop-based sugars 

Fermentation is already changing how food and bio-based manufacturing are imagined. Microbes can be used to produce specific compounds with precision, efficiency and a smaller physical footprint than many conventional production systems. 

The sustainability of fermentation, however, does not depend only on what microbes produce. It also depends on what microbes consume. 

Most microbial production systems still rely on sugars from agricultural crops. At industrial scale, these feedstocks shape the environmental and economic footprint of the entire process, influencing land use, water use, agricultural inputs and the resilience of supply chains. 

Formate offers a possible alternative because it can be made by electrically reducing CO₂, allowing captured carbon and renewable electricity to become inputs for microbial production. In principle, this means future bioprocesses could feed microbes with carbon compounds made from CO₂ rather than sugars grown on farmland. 

Unlocking hidden fungal metabolism 

The Imperial team focused on Yarrowia lipolytica, a yeast with strong industrial potential. It is already valued as a robust production host and has been explored for making lipids, organic acids, terpenoids and food-related additives. 

Until now, no known yeast has been able to grow on formate as its only carbon source. This has limited the use of fungi in one-carbon biotechnology, even though yeasts and other fungi have important advantages for industrial production. 

Using metabolic modelling, carbon-tracing experiments, adaptive laboratory evolution and metabolic engineering, the researchers investigated whether Y. lipolytica could be taught to use formate. 

They first found that wild-type Y. lipolytica already had a hidden ability to use formate when grown with glycerol. This suggested that the yeast possessed a cryptic metabolic capacity that could be activated and redirected. 

Through model-guided adaptive laboratory evolution, the team then produced a strain able to grow on formate alone. The evolved strain used a eukaryotic serine–threonine cycle to incorporate carbon from formate into biomass. 

From lower land demand to useful products 

The study did not only show that the yeast could grow on formate. The team also demonstrated that engineered Y. lipolytica could produce beta-carotene from formate, providing an early proof of concept that carbon-derived feedstocks can be converted into useful products. 

Beta-carotene is a valuable antioxidant and colour-associated compound with relevance to food, nutrition and biomanufacturing. Its production from formate suggests that one-carbon feedstocks could eventually support the manufacture of ingredients and compounds that currently depend on more conventional production routes. 

This is the broader significance of the work. A fermentation industry that is less dependent on crop-based sugars could help produce future food ingredients, alternative proteins, nutrients, colours, lipids, materials and chemicals while reducing pressure on farmland and agricultural resources. 

For sustainable food innovation, the importance lies not only in the quality of the final product, but in the sustainability of the system used to make it. Future fermentation-derived ingredients will need to scale in ways that are affordable, resilient and less demanding on land. 

“Sustainable food innovation is not only about what we produce, but how we produce it. Developing microbes that can use alternative carbon sources is an important step towards more resilient and sustainable biomanufacturing.”  Professor Rodrigo Ledesma-Amaro

Managing the challenge of formate 

Formate is promising, although it is not an easy feedstock for cells to use. The study found that formate can create oxidative stress, disrupting cellular energy metabolism and producing reactive oxygen species that can damage the cell. 

The evolved strain appeared better able to manage this stress and maintain mitochondrial function. The researchers then engineered pathways linked to NADPH and reactive oxygen species metabolism, improving growth and showing that formate-based biomanufacturing will require a careful balance between carbon assimilation, energy generation and cellular stress management. 

The best-performing strain reached around 10% of the theoretical maximum biomass yield. This result shows clear potential, while also making clear that further engineering and process optimisation will be needed before industrial application. 

Future work will need to improve growth rates, yields, product titres and culture conditions, including oxygenation, pH and feedstock delivery. 

Towards fermentation beyond farmland 

The findings add to growing evidence that fungi could become powerful platforms for one-carbon biotechnology. 

Bacteria have been explored extensively for converting CO₂-derived compounds into useful products, while yeasts and other fungi offer distinct advantages of their own. They are often robust, scalable and capable of producing compounds that are difficult to make in bacterial systems. 

The study also suggests that the serine–threonine pathway used by Y. lipolytica may be widespread across fungi. This raises the possibility that other single-celled fungi could be engineered for similar forms of carbon assimilation. 

For the sustainable protein and microbial food sectors, this could open new routes to making food ingredients, nutrients, colours, lipids and other high-value products from carbon-derived feedstocks rather than conventional agricultural inputs. 

The science remains early, yet the direction is compelling. If biology can be engineered to connect CO₂, renewable electricity and microbial production, the future of fermentation could be less tied to farmland and more closely integrated with circular carbon systems. 

One day, single-celled fungi may help turn CO2 efficiently into the ingredients and materials that sustain everyday life.