What’s brewing? Precision food proteins from fermentation

By Dr Thomas Vanhercke, Dr Michelle ColgraveJanuary 25th, 2022

Precision fermentation has emerged as one of the frontrunners for additional sources of protein that could underpin the growth of a sustainable bioeconomy in Australia. We explain current trends and future research priorities.

To feed the global population of the future, we will need to produce food at a greater scale, and more sustainably, than today.

To meet that gap, well need to derive even more protein from traditional sources (meat, dairy, eggs, seafood, plants) in addition to protein from emerging but complementary sources (yeast, fungi, algae, insects). Precision fermentation (PF), a relatively new field of biotechnology, has emerged as one of the frontrunners for additional sources of protein that could underpin the growth of a sustainable bioeconomy in Australia.

Precision fermentation uses the same fundamental principles of fermentation that has a long and safe history in supplementing and diversifying our foods.

How precision fermentation works

Traditional fermentation processes rely on microbial cells (yeast, fungi) and anaerobic (oxygen-free) conditions to convert ingredients into end-products with unique texture or flavour properties such as yoghurt, bread, cheese, tempeh, and alcoholic beverages.

Biomass fermentation, on the other hand, makes use of the nutritional qualities of fungal mycelium, and the branching thread-like fibres that typically form the vegetative part of a fungus. Mycelium are cultivated in large tanks, with sugar and other nutrients added to trigger growth. The mycelium is harvested, then cut and flavoured to produce alternative protein products (mycoprotein). Fungal mycelia offer high levels of protein as well as fibre, vitamins, minerals, and can be used directly as an ingredient, without the need to extract and purify the protein.

One example is the mycoprotein derived from the fungus fusarium venenatum which was pioneered in the late 1960s and has been sold under the brand QuornTM since 1985. Since then, other mycoprotein start-ups have emerged around the globe, such as Fable Foods (Australia), Meati, Prime Roots and Nature’s Fynd (USA), Mushlabs (Germany), and Kinoko-Tech (Israel).

Nature’s Fynd FyTM protein, for example, is derived from a different fusarium strain flavolapis, discovered from the hot springs of Yellowstone National Park. Products such as FyTM protein can serve as an ingredient for dairy-free or meat-free foods.

Consumer and sustainability benefits

Today, PF is being harnessed to synthesise compounds that would otherwise be too expensive and/ or complicated to harvest from their natural sources. While traditional and biomass fermentation involve propagation of microbial cells without any genetic modification, PF relies on reprogramming microbes to produce specific, customised (recombinant) molecules that can serve as new food ingredients.

By introducing the genetic information that codes for specific proteins into the microbial genome, cells can be programmed to act as highly efficient cellular factories that can grow on a variety of carbon sources and deliver desired outputs, which are typically proteins equivalent to those found in nature.

The novel products obtained via PF technology can enhance consumer products by improving taste, texture, or other functional aspects to accommodate consumers preferences and sustainability concerns.

A well-known historical example of a high-value food protein derived from PF is chymosin, the major enzyme in calf rennet used during cheesemaking. In fact, by 2006 fermentation-derived chymosin occupied as much as 80% of the global market share for rennet.1

Many proteins, many companies

Eden Brew’s milk prototype

In recent years, significant advances in the field of genetic engineering have allowed for rapid reprogramming of microorganisms (synthetic biology) to produce a whole suite of specific food protein ingredients in a cost-efficient and sustainable manner. In the wake of the early chymosin application, PF is now increasingly being used to deliver specific ingredients for adjacent industries.

For instance, PF-produced soy leghemoglobin, a key ingredient in the plant-based ImpossibleTM burger that is responsible for imparting the unique colour and taste of meat, was recently approved by Food Standards Australia and New Zealand (FSANZ, Application A1186). Other examples of start-ups built on PF technology include the Every company (egg protein), and a raft of companies in the dairy alternative space including Perfect Day (casein and whey dairy proteins), Eden Brew (milk and dairy), Formo and Change Foods (cheese).

New synthetic biology companies such as Nourish Ingredients (animal lipid flavours) and Motif Foodworks are developing flavour alternatives to further improve the overall quality of next-generation alternative protein products.

Precision fermentation challenges and opportunities

The opportunity of producing tailored food ingredients by PF has not gone unnoticed to investors. During the first seven months of 2020, PF attracted a total of US$435 million in venture capital investment. This has catalysed a wave of food fermentation companies.2 Motif Foodworks and Perfect Day are leading the way, raising US$200-300 million during their latest funding series in 2020-2021,3 while the Australian PF start-up Nourish Ingredients secured US$11 million in seed funding in 2021.

Despite the growing interest, several challenges remain for this emerging industry. Most PF start-ups are still at a relatively nascent stage. Fermentation infrastructure with the capacity to operate at scale is severely limited, highlighting the urgent need for investment in larger scale fermentation and downstream processing facilities.4

Early implementation of techno-economic analyses is needed to assess overall economic viability during scale-up and to identify critical factors that determine the cost of goods. Similarly, sustainability and carbon footprint claims related to specific PF production processes will need to be supported by rigorous independent life cycle analysis, such as recent studies conducted by Perfect Day and Impossible Foods.5,6

Regulatory approval frameworks with regards to synthetic biology and PF are currently being revised in many jurisdictions, including FSANZ,7 to keep up with technological innovations such as genome editing.

Consumer perceptions related to novel PF-derived food products and appropriate labelling will require social licence to ensure continued trust and transparency.

Precision fermentation relies on the production of novel proteins or protein ingredients by:
1. Growing microbes on a cheap carbon source (feedstock) such as sugar
2. The microbial cells themselves are genetically modified to produce the desired protein in high quantities. Typically, this engineering step requires multiple cycles where required genetic changes are predicted, designed and introduced into the DNA of the cell. This is followed by testing for the presence of the target protein, validation of the desired food property and further genetic improvements to increase product quantity and quality. This rapid and often complex ‘design-build-test-learn’ engineering process is defined as ‘synthetic biology’ and happens in small reactors in the lab
3. The next step is a gradual scaling-up of the culture volumes from lab (tens of litres) to commercial scale (order of hundred thousand litres) 
4. Depending on the application, the proteins are extracted, purified and combined (formulated) together with other ingredients into,
5. The final food product. Summarised in the lower half are the challenges and opportunities where future process improvements are likely to drive down overall R&D and production costs as precision fermentation continues to mature as a scientific field.

Future research priorities

Future research will focus on improving the overall cost effectiveness of PF processes to achieve higher product yields. Improvements in cellular secretion machinery will simplify downstream purification and, in turn, improve capital utilisation and lower costs.

Novel naturally occurring and under-utilised microbes or next-generation microbial strains will be investigated for their ability to thrive on abundant and cost-effective feedstocks, to replace refined sugar by various (food) waste streams and even CO2 (e. g. Air ProteinTM).

New artificial intelligence/machine learning (AI/ML) algorithms will offer the opportunity to drastically speed up the engineering of new microbial production strains by relying on computer models that can simulate the effect of specific genetic changes on overall cell behaviour and composition (metabolism).8

Advances in AI/ML are also breaking ground in the prediction of ingredient combinations that result in new flavours (NotCo), the engineering of sweeteners with novel properties via computational protein design (Amai Proteins), and screening for novel protein functionalities using large food-safe protein databases (Protera).

Continuing innovation in bioreactor redesign tailored for food-grade fermentation is required and these systems will need to be powered by renewable energy resources to deliver their full impact potential.

Minimising purification/processing and maximising value extraction from left-over microbial biomass through the delivery of co-products during downstream processing will improve the overall economics of PF technology.

Overcoming the challenge of scale

Fermentation, in its various forms offers an exciting opportunity to deliver optimised nutrition and improved flavour or functionality, especially when incorporated with other food segments.

In addition to specific ingredients, technology platforms like PF can deliver enzymes that can be used as food processing aids such as those used for tenderising meat.

Over time, the costs associated with PF will continue to decline, and PF-derived products will reach cost-competitiveness with a wider range of traditional materials.9

Australia has a unique advantage to enter this emerging industry given the easy access to abundant and cheap sugarcane, crushing infrastructure and access to ports for export to Asian markets.10

Yet the need to scale the production systems, combined with implementation of renewable energy sources, will be critical to the successful establishment of the industry.

This article was originally published in AIFST Food Australia Journal. Republished with permission.

References

  1. Johnson, ME, Lucey, JA (2006). “Major technological advances and trends in cheese” Journal of Dairy Science, 89: 1174-1178.
  2. Specht, L, Crosser, N (2020). “State of the industry report. Fermentation: An introduction to a pillar of the alternative protein industry” The Good Food Institute https://gfi.org/blog/fermentation-stateof-the-industry-report/
  3. Crosser, N (2021). “2020 State of the industry report. Fermentation: Meat, eggs, and dairy” The Good Food Institute https://gfi.org/resource/fermentation-state-of-the-industry-report/
  4. Warner, M (2021). “Commercial fermentation: opportunities and bottlenecks” https://gfi.org/event/commercial-fermentation-opportunitiesand-bottlenecks/
  5. Sinistore, J, Lab, J, Natarajan, M, Kriete Z (2021). “Comparative life cycle assessment of Perfect Day whey protein to total protein in milk” WSP USA https://f.hubspotusercontent00.net/hubfs/7692102/Comparative%20Perfect%20Day%20Whey%20LCA%20report%20prepared%20by%20WSP_20AUG2021_Non%20Confidential-1.pdf?hsCtaTracking=2df1505b-f8f6-4242-9192-495d0f428c0f%7C1301fe86-ab41-4f1a9d5f-b61e8bbf3658
  6. Khan, S, Dettling J, Loyola C, Hester J, Moses R (2019). “Environmental life cycle analysis: Impossible burger 2.0” Quantis https://impossiblefoods.com/sustainable-food/burgerlife-cycle-assessment-2019
  7. Food Standards Australia New Zealand (2021) “Proposal P1055 – Definitions for gene technology and new breeding techniques” https://www.foodstandards.gov.au/code/proposals/Pages/p1055-definitions-for-gene-technology-and-newbreeding-techniques.aspx
  8. Lu, H et al. (2019). “A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism” Nature Communications, 10:3586
  9. Tubb, C, Seba, T (2020). “The roadmap to disruption and market opportunities” Rethinx https://rethinkdisruption.com/the-roadmap-to-disruption/
  10. CSIRO Futures (2021). “A national synthetic biology roadmap: identifying commercial and economic opportunities for Australia” CSIRO, Canberra https://www.csiro.au/en/work-with-us/ services/consultancy-strategic-advice-services/csiro-futures/futures-reports/synthetic-biology-roadmap.

Dr Michelle Colgrave leads the CSIRO Future Protein Mission, a large research initiative aimed at capturing growing demand for high quality and sustainable protein. Michelle is also a Professor of Food and Agriculture Proteomics at Edith Cowan University. Dr Thomas Vanhercke leads the Novel Protein Production Systems and Agriculture and Food domains within the CSIRO Future Protein Mission and CSIRO Synthetic Biology Future Science Platform, respectively. Thomas background is in plant and yeast synthetic biology with a particular interest in food proteins and lipids.

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