s41467 023 37891 1 PDF
s41467 023 37891 1 PDF
1038/s41467-023-37891-1
Our current food system relies on unsustainable practices, which often fail to
provide healthy diets to a growing population. Therefore, there is an urgent
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demand for new sustainable nutrition sources and processes. Microorganisms
have gained attention as a new food source solution, due to their low carbon
footprint, low reliance on land, water and seasonal variations coupled with a
favourable nutritional profile. Furthermore, with the emergence and use of
new tools, specifically in synthetic biology, the uses of microorganisms have
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expanded showing great potential to fulfil many of our dietary needs. In this
review, we look at the different applications of microorganisms in food, and
examine the history, state-of-the-art and potential to disrupt current foods
systems. We cover both the use of microbes to produce whole foods out of
their biomass and as cell factories to make highly functional and nutritional
ingredients. The technical, economical, and societal limitations are also dis-
cussed together with the current and future perspectives.
The current food systems have been pushed to a crisis, as they struggle the food industry19–21. Moreover, using fermentation to produce
to keep up with nutrition and protein demand coupled with population microbial biomass as a nutritional food source is starting to be adopted
growth1. All our food systems—agriculture, animal husbandry and in both animal feed and human foods22–24. However, there are challenges
aquaculture—are grappling with the degradation of land, climate to overcome in each of these applications, including scalability and
change and climate disasters, which are set to rise in the future2. economic or ecological sustainability. Novel tools can be applied to
Although moving towards plant-based foods is less environmentally these fields to enhance and accelerate the development of microbial-
harmful, it still relies on climate or season and intensive land, water and based foods and overcome current limitations. This includes high-
chemical use3. The time for a microbial revolution in food is ripe as resolution and high-throughput characterisation of microorganisms14,25,
microorganisms have the potential to enhance, improve or even as well as genetic and metabolic engineering tools4. By engineering and
replace the currently available alternatives4,5. They have been proven to selecting strains, it is possible to improve flavour26 and nutrition20,27,28 as
be an ecological and resilient food source, especially when compared well as increase sustainability using waste feed or cheap non-competing
to traditional protein sources such as meat6,7. Genetic and system carbon sources8,29. This can contribute to increasing applications and
design can advance sustainability further when renewable and waste uptake to propel a microbial revolution in food.
feedstocks are considered8,9. Furthermore, they are highly resilient due Due to the high potential and varied applications of microbes in
to their decentralised nature that does not rely on location limitations, food, there have been numerous recent start-ups in this space, ranging
such as temperature or weather10. Finally, they also have a high nutri- from improving traditional fermentation to creating new products
tional profile11, crucial in the face of rising diet-related health epidemics. (Table 1). Development is still needed for technical advances and
Microorganisms are no stranger in the history of food; however, consumer acceptance but the field of single-cell proteins and engi-
research has lately revealed the vast array of health benefits and eco- neered microbes in food has high potential, as will be explored in this
logical savings that can be derived from using microorganisms in review. This review aims to give an overview of the different applica-
food12,13. This has led to an explosion in new applications, improvement tions of microorganisms in food ranging from traditional fermentation
in traditional practices using state-of-the-art technology14–16 and a better techniques to biotech applications of ingredient production (see
understanding of their roles and benefits13. Fermentation can be used Fig. 1). It covers the different novel applications of microbes in the food
both directly on foods to improve nutrition, taste or texture17,18, as well system as well as the role of synthetic biology in advancing this field.
as used as a production platform to produce value-added ingredients in Finally, the obstacles and future perspectives will be considered.
1
Department of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK.
e-mail: [email protected]
Table 1 | Start-ups and companies developing microbial food either for humans or animal feed as well as individual compo-
nents or flavourings used
Fig. 1 | Timeline of the role of microbes in food. A view of the various applications as the current or potential role of genetic engineering and other future develop-
that rely on microbial processes. State-of-the-art in each process is explained as well ments to enhance the process or use.
The use of microbes in food and salting, fermentation was a primary method of food preserva-
Rise of fermentation in history tion and thus a crucial technology in the rise of human
Microorganisms were first leveraged by humans in the food system civilisations32. In addition, the process also introduced many new
for fermentation. Fermentation is one of the earliest known food products, flavours and tastes. Different fermented products rose
technologies dating as far back as 7000BC or earlier and arising from specific environments and conditions which produced a
independently in multiple ancient cultures30,31. Alongside smoking diversity of edible products32. These include, but are not limited to,
dairy products such as cheese and yoghurt, alcoholic products such improve the nutritional value of food by interfering with anti-
as beer and wine, fermented bean products such as soy sauce, nutritional factors, which impede protein, carbohydrate or
douchi (豆豉) and natto, other vegetables such as sauerkraut and phytochemical availability. For example, trypsin inhibitors found
kimchi and many more32. abundantly in various cereals, grains and legumes have been
The advent of new processing and preservation methods such as shown reduced activities in fermented foods42.
refrigeration, the use of natural and artificial preservatives, and 3. Reducing Glycaemic Index: The Glycaemic Index (GI) measures
freezing and vacuum sealing, among others, have provided alter- how quickly carbohydrates in food raise blood glucose levels43.
natives to traditional fermentation. However, more recently, research Probiotic and/or fermented cereals, pseudo-cereals and dairy
has brought to our attention the many health benefits offered by a products have been linked to a reduction in the GI of the food and
microbial presence in food13,33, causing a resurgence in popularity, and the blood sugar response43,44. Lowering GI intake and response
many newly popularised health foods are fermented or have fer- has been shown to reduce risk factors for diseases such as type II
mented ingredients. This is compounded by the rise of plant-based diabetes and cardiovascular disease43.
diets and increasing access to international foods—many of which 4. Removing toxins: Microbial consortia can also act by removing
include traditionally fermented products. A good example is Kombu- toxic compounds and inhibiting the growth of pathogenic spe-
cha, a traditional Manchurian fermented tea drink which was intro- cies. For example, Aflatoxin, a common toxin found in foods
duced to the international market with many purported health benefits contaminated with Aspergillus flavus, has been shown to be
and now is valued at over 1 billion US dollars34. Other well-known enzymatically reduced in various fermentative processes45. Free
examples are Tempeh and Tofu, two fermented soybean products radicals in vegetable and fruit products are also reduced during
from Indonesia and China, respectively, which are now consumed as fermentation46.
meat-alternative protein sources globally35. 5. Biochemical pathways producing health-promoting compounds:
Many microorganisms naturally produce nutritionally beneficial
Different functions and health benefits of fermented foods chemical compounds including but not limited to antioxidants,
Fermentation, in the context of food, refers to raw material under- polyunsaturated fatty acids, conjugated linoleic acids (CLA),
going enzymatic conversions in the presence of microorganisms13,36. sphingolipids, vitamins and minerals4,47,48.
These conversions result in alteration in their physicochemical prop-
erties. Many of the resulting metabolites play an active role in food However, fermentation does not always improve the foods and
preservation, inhibiting the growth of contaminating or spoiling undesired microorganisms can negatively impact some nutritional
pathogens and increasing shelf life, but others contribute to nutrition, aspects. Some examples include the production of toxic biogenic
texture, taste and smell13. Depending on their composition, fermented amines by lactic acid bacteria35, including an increase of free histamine
food may also bring health benefits. The list is a brief summary of some due to the high presence of histidine-producing enzymes (L-histidine
of the most relevant benefits, although comprehensive reviews can be decarboxylase) in microorganisms49. To counteract this, strategies
found on the topic18,37: have been developed to either optimise strain selection50 or use
1. Microbiome enhancing (or probiotic) qualities: The gut micro- engineered strains to enhance biogenic amine degradation51. Finally, it
biome is increasingly proving to be crucial for maintaining is also worth noting that many health claims related to fermented
health38. The use of probiotics supplements has become widely foods are yet to be fully verified by randomised controlled trial studies
adopted, although the health benefit and strain formulation and have often been exaggerated for marketing purposes52.
remain controversial topics39. The consumption of certain fer-
mented foods themselves has proven to have probiotic and The nutritional profile of microbes
health-promoting effects40. Microbial biomass itself also often has qualities that lend itself to
2. Increasing bioavailability of nutrients in food: This is due to consumption as food, including high protein, fibre and bioactive
microorganisms breaking food down for easier digestion and compound content (see Fig. 2).
absorption of ingested nutrients. For example, lactic acid fer- All microorganisms are generally characterised by high protein
mentation can increase the food’s iron content by optimising pH content, with algal species averaging between 40–60%, fungi 30–70%
and acid content for solubility41. Similarly, fermentation can and bacteria averaging between 53 to as high as 80%11,12. Furthermore,
Fig. 2 | Nutritional profile of microbes. The left panel shows the various com- compounds. The right panel shows the relative levels of fibre, protein and micro-
ponents of microorganisms that are beneficiary for nutritional needs. This includes nutrients in four groups of microorganisms commonly used for food applications
both macro-molecular elements such as proteins and fibre as well as small bioactive based on comparisons from the review by Ravindra11.
many species are complete amino acid sources, containing adequate microbial consortia, including those found naturally in foods, as has
amounts of essential amino acids which humans cannot synthesise and been reviewed in previous works68,69. In addition, in the last years,
need to acquire from diet53. In addition, many microbes have a high synthetic biology tools specifically developed to engineer microbial
content of essential amino acids that are lacking in plants54. communities have been created70, which have the potential to be used
Fibres, resistant carbohydrates that are key in maintaining gut to improve food manufacturing. This includes spreading metabolic
health55, are also elevated in many microbial species11. Algae, for burden such as when two strategies to reduce browning in soy sauce
instance, has a high fibre content that is composed mainly of insoluble production were engineered to act synergistically in two microbial
fibres, cellulose and other polysaccharides found in their cell walls56. species71, or enhancing natural coculture properties, such as increasing
Both filamentous fungi and yeast have potentially beneficial fibres, quorum sensing mechanisms which reduce food spoilage72.
namely β-glucan and mannan-oligosaccharides, both of which are
consumed as health supplements for gut health and immune-boosting Use of microbes as a protein source in human food
effects57,58. The use of microbes as a food ingredient is known as single-cell protein
Although lipid content is generally low compared to animal pro- (SCP) and usually refers either to dried or processed microbe biomass
ducts, oleaginous yeasts and algae are a source of high-value dietary or to the proteins extracted from it. It can be ingested either as a
lipids, especially long-chain polyunsaturated fatty acids34,59. Interest- supplement, ingredient or as a main food source (see Fig. 1). Thanks to
ingly, the overall calorie content can be quite low, such as in com- its potential for sustainable fermentation8,28 and its favourable nutri-
mercially available nutritional yeast flakes, which contain 400 calories tional profile11, it has the potential to become a large component of
per 100 g, bringing a high ratio of nutrition to energy. Finally, micro- our diet.
organisms often have high endogenous contents of nutritionally SCP has a long and varied history, beginning before the World
relevant compounds, including vitamins, minerals, antioxidants and Wars and continuing into the late and mid 20th century73,74. However,
other functional ingredients11. most projects were discontinued in the face of rising energy costs and
The nutritional profile of microorganisms requires further inves- the success of the green revolution, although some legacies remain75.
tigation as their use becomes more widespread. The true digestibility One of the first of these is Marmite, established in 1902 as a by-product
of the elements discussed above has not been fully elucidated11 and the of the beer industry has even been consumed as an army ration as a
compositions can differ widely based on different species and the source of B vitamins61. Since then, there has been development in
environments in which they are grown60. Species need to be carefully other, more texturised SCPs—notably that of Quorn. Quorn, estab-
selected as some microorganisms also have significant safety and lished in the 1980s, produces SCP from the filamentous fungi Fusarium
health detriments. An elevated RNA content is often seen in micro- venenatum and then treated to remove excess nucleic acid content and
organisms which can lead to health issues, such as gout and kidney finally texturized to create meat replacements76. It is now a widely
stones61. Some fungal and bacterial species also produce allergens and distributed product sold in 17 countries with a reported revenue of 236
toxins and are thus ill-suited as food or require processing before million GBP in 2020. SCPs are also consumed as a health supplement,
ingestion11. By carefully choosing species, substrates, and conditions, such as the microalgae Chlorella and Spirulina, which are rich sources
the nutritional aspects of the food can be modulated to suit of proteins as well as phytonutrients and vitamins77.
specific needs. Given the ecological and nutritional benefits of SCPs, there is a
renewed demand which has resulted in research into new sources of
New technologies and applications for microbes in SCPs as well as novel cultivation methods. There is a profusion of start-
human food up companies trying to bring new SCP products to market with some
Enhancing fermentation examples listed in Table 1, with many start-ups focussing on meat
Fermentation can be optimised by specially selecting, breeding or alternatives.
engineering strains of microbes to enhance the appearance, taste or So far, most research has focused on wild-type (non-engineered)
health profile of fermented foods18,62,63. Traditionally, breeding and strains, which have been selected based on their protein content and
selection techniques were used to select for favourable qualities even whose production have been optimised manipulating growing condi-
before the biology of microbes was discovered, leading to vastly dif- tions. Synthetic biology has the potential to engineer selected strains
ferent strains for specific uses30. Using genetic profiling techniques and to further improve protein production, which can be achieved by (1)
-omics technology, we are now able to further identify strains with enhancing and expanding the capacity to efficiently use desirable
favourable properties14,15. Large-scale analysis has also enabled the feedstocks, (2) improving yields for biomass and protein production
identification of strains with desired aromas, which were further and (3) adding functionalities to the single-cell protein by the co-
improved by hybridisation techniques16. production of valuable compounds such as vitamins or antioxidants78.
More recently, fermentation has been enhanced by using genetic Improving growth and substrate use can greatly improve ecological
engineering, where strains used in traditional fermentation can be and economical aspects, for example, by transforming waste into
manipulated to produce additional beneficial products. Some exam- proteins79.
ples of modifications include the enhanced production of B vitamins in
Lactobacilli used in dairy products63,64 or the synthesis of aroma Animal meat alternatives
compounds in S. cerevisiae strains for novel and improved beer Microbes are a promising substitute for meat products. This is thanks
flavours65. to their matching protein and nutrient levels, as well as their potential
Genetic engineering has also been used to improve the sustain- to be modified and texturized to resemble meat.
ability of the fermentative food processes, which can be achieved by One of the most established companies is Quorn, which produces
expanding or improving substrate range and utilisation22,66,67 This SCP derived from filamentous fungi. Quorn has products that resem-
furthers the potential to use waste feedstocks8,9 and move towards a ble meat products from chicken nuggets to beef mince and has a large
fully circular economy. selection of different textures and forms it comes in refs. 80, 81. To
It is worth noting that many fermentation processes are carried achieve this, the long strands of hyphae are mixed with binding agents
out by microbial communities rather than single strains, which adds an and then this fibre–gel complex is freeze texturised which allows for
additional layer of complexity to the understanding and limits our hyphal laminations that recreate the fibrous texture of meat80. Other
capacity to improve them. Advances in sequencing technologies and start-ups including Meati Foods, Mycorena and Nature’s Fynd are also
systems biology have allowed us to improve our knowledge of producing meat analogues from filamentous fungi.
Besides mimicking the nutritional profile or protein content, meat niger, which has allowed many kinds of cheese to become suitable for
flavourings can also be produced by microbes. These products can be vegetarians as well as reducing the price, benefiting cheese makers94.
extracted and purified, or the whole microbial biomass can be used.
For example, in the Impossible burger, Pichia pastoris is engineered to Microorganisms in animal feed
produce soybean leghaemoglobin c226, which recreates part of the The use of microbes in animal feed first appeared over a century ago
flavour profile of meat. The engineered microorganism is then incor- when brewery by-products were used to supplement feed by Max
porated with other ingredients including soy and potato proteins. Delbruck. More recently, using microorganisms as a main or supple-
Haemoglobin is also being produced as a stand-alone ingredient to add mental nutritional source has become established as an industry norm
to plant-based meats, such as in the start-up Motif Foodworks. In in both animal agriculture95 and aquaculture23. This is due to an
academia, there is a concentrated effort to produce many variations increase in regulatory ease and technological capabilities as well as
of haemoglobin proteins which could account for future taste growing pressures for cost and ecological efficiency96.
expansions82. Other individual components of meat can also be pro- Many different microbial species have been investigated for the
duced, such as the structural elements gelatine and collagen83,84. benefits in both animal health and production output23,24. Different
Finally, one main challenge of recreating meat is providing an microbial species each have their own limitations and advantages and
adequate lipid composition and content. Most plant-based alternatives thus need to be matched to desired functions and livestock23,24. Fur-
utilise plant oils, which have a strongly differing taste and mouthfeel. thermore, there are different delivery options- including as a
The endogenous contents of lipids in microbes also differ significantly sole nutritional source23, as nutritional additive24 or can act as
from that of meat; however, there is vast academic research on pro- probiotics97,98.
ducing dietary lipids in microbes. Oleaginous species have been found Live microbial supplements can act as probiotics and can either be
to be a suitable production platform for highly nutritious fatty acids, species delivered to colonise the gut and integrate to improve the
such as omega-3 fatty acids which are found abundantly in fish27. existing microflora, or to help balance the existing microbiota by
Furthermore, advancement in the production of microbial oils gives us modulating the pH, feed existing microorganisms and to defend
the potential to not only tune lipid composition but to also modify against pathogenic species. Using probiotics in animal feed is
fatty acids to become more suitable for animal replacement uses85. becoming an industry norm as it has large therapeutic gains while
Little focus has been given to mimick animal fats in academic research, reducing the need for drugs and antibiotics. In addition, the use of
although start-ups such as Melt & Marble and Nourish Ingredients aim probiotics is shown to improve feed uptake, immune response and
to make dietary fats for animal replacements through fermentation. stress tolerance97–99. It has also been linked to increased growth, bio-
mass and milk production97.
Other animal product alternatives The new generation of SCP-based animal feed uses engineered
Engineering microbes also have the potential to recreate animal pro- microorganisms nutritionally tailored to the target animal28,78,100.
ducts such as dairy and eggs. This is done through precision fermen- Moreover, it can be also employed as a nutraceutical and therapeutic
tation, where the pathways of individual components have been platform such as in the previously commercial omega-3 enriched
engineered into microorganisms. Yarrowia biomass employed in Verlasso® salmon101, and the efforts in
Milk is composed of oligosaccharides, fats, sugars and proteins, the start-ups such as Cyanofeed (see Table 1). Vitamins, fatty acids and
primarily that of casein and whey4. These various components are phytonutrients have been successfully delivered through feed28.
being reproduced using synthetic biology in microorganisms4. Finally, engineering organisms to utilise waste substances as carbon
The main milk proteins, namely casein proteins and whey proteins, sources can greatly lower the ecological footprint of highly polluting
have been successfully engineered into various organisms, including animal agriculture industries28,29.
bacteria and yeasts4. These technologies are being employed by var-
ious start-ups developing animal-free milk, such as Perfect day, Better Precision fermentation of food ingredients and
Dairy and Formo, which use purified milk proteins extracted from additives
microbial cell factories and mixed with other fats and sugars. One of the most developed uses of engineered microbes in our current
Human breast milk has also been researched as it is thought to food ecosystem is the production of ingredients and additives. For
have important effects on the development of the neonatal gut flora decades, microorganisms have been selected and improved to max-
and immune system86. Components such as milk fats and milk oligo- imise the synthesis of molecules of interest, first by random muta-
saccharides have been developed with precision fermentation for genesis and selection and then by genetic and metabolic engineering
human breast milk, both in academia as well as in industry, such as by in a practice called precision fermentation16,21. A paradigmatic example
the SME Conagen. Human milk oligosaccharides (HMOs) have been is the production of vitamin B2, where chemical synthesis was sub-
produced in both S. cerevisiae and B. subtilis87 and human milk fats in stituted by fermentation in the 90s102. The yields and productivities of
the oleaginous yeast Y. lipolytica88. The probiotic effects can also be the processes are key to determining economic feasibility and there-
mimicked by recreating the microbiome of breast milk through the fore, metabolic engineering is playing an important role not only in
addition of microbial populations to formula89. The actual effects of increasing yields but also enabling the production of heterologous
these supplements would benefit from further studies in humans. chemicals22. Interestingly, the use of genetically engineered strains to
Eggs have a larger and more complex group of proteins that are produce specific compounds is generally well accepted by consumers.
responsible for their unique texture and taste. However, there have This is because, by the end of the fermentation process, the molecules
been efforts to recombinantly express different proteins, initially for of interest are extracted and purified. They are therefore typically free
allergenicity and protein studies90,91, and more recently as food of recombinant cells or DNA, allowing them to be labelled as natural
ingredients92,93. Furthermore, there have also commercial efforts to products103.
produce egg alternative products made up of multiple egg proteins. While most nutraceuticals and additives with health benefits are
This includes the start-up EVERY, which launched an egg white product still made by chemical synthesis or plant extraction, an increasing
made from recombinantly produced proteins in 2021. number of them are now bio-manufactured by microorganisms4. Some
One animal-based ingredient that has already been largely of these nutraceuticals include water-soluble vitamins (vitamin B
replaced by precision fermentation is rennet, an enzyme mixture con- complex and vitamin C) as well as fat-soluble vitamins (vitamin A/D/E
taining chymosin found in the lining of the stomach of young rumi- and vitamin K)20. Other nutraceuticals made by engineered microbes
nants. Commercial chymosin is now mostly produced in Aspergillus have been reviewed elsewhere21, and the list includes omega-3 fatty
Meat
Alternatives
Enhanced
flavour and
Economic odours
viability Improved nutrient Ultimate
& health nutrition
RNA content properties foods
Consumer Growth on
acceptance Waste
Food for
difficult to Widespread use
reach
areas of Microbial foods
Fig. 3 | The future of microorganisms in food. A schematic showing the obstacles developments, shown in the blue arrow, aim to improve microbial-based foods and
and future developments in the path to adopting widespread use of Microbial overcome these obstacles, and include producing nutritionally complete whole
foods. In the beige circle the main obstacles are shown, including the economic foods, alternatives to animal products (meat, dairy, eggs), and ingredients (like
viability of some processes, the consumer acceptance of some products, especially flavours or nutraceuticals) that can be made in an affordable and sustainable way,
GMOs and, in some cases, the presence of undesired molecules. Future perhaps using waste or CO2 as carbon sources.
acids, polyphenols such as resveratrol and naringenin, carotenoids As a sole food source, the odours and textures of pure microbial
such as beta-carotene or Astaxanthin, and non-proteinogenic amino cell mass have been postulated to be unsuited to human palate,
acids such as GABA and beta-alanine. Other ingredients made by however this setback could be improved through breeding or engi-
microbes are intended to improve the organoleptic properties of the neering in taste with genetic modifications or by creating mixtures or
food to which they are added to, improving taste, odour, colour and co-cultures to have novel and pleasant tastes16,115.
feel. Flavour enhancers such as glutamate (MSG), inosine monopho- Many microorganisms, especially yeast, fungal and algal clades
sphate (IMP) and guanosine monophosphate (GMP) are made by also have thick cell walls. In many cases, this is an important con-
microbes and contribute to the desired umami flavour104. Microbes tributor of fibre in the diet. However, for some SCP, the thick cell wall
have also been engineered to produce sweeteners such as stevia- can limit the number of nutrients that can be taken up and can itself be
derived molecules, xylitol or erythritol105–107. More exotic, hoppy fla- indigestible. Therefore, it may be necessary to treat the SCP using heat
vours have been engineered into yeast to make tastier beer65. Odours and/or mechanical and enzymatic processes, improving nutrient
and aroma compounds have been made by microbial processes like bioavailability114.
those of rose (2PE)108, orange/lemon (limonene)109, mint (menthol)110,
peach (gamma-decalactone)111, among many others. Food safety
In addition, coloured molecules have been synthesised by Microbial-based foods and ingredients must go through regulatory
microbes with the intention to be used as pigments for food and approvals, which are stricter when new or engineered species are used.
beverages. Some examples include orange (beta-carotene, can- Regulatory bodies assess safety and authorize foods in a country-
thaxanthin), red (lycopene, astaxanthin, prodigiosin), yellow specific manner. For example, the FDA and EFSA are the main reg-
(riboflavin), blue (phycocyanin), purple (violacein) and black (mel- ulatory bodies in the USA and Europe, respectively. Some strategies to
anin) colourants19. facilitate the obtention of approvals for microbial foods include the
use of approved organisms and processes, limiting the application to
Obstacles and future perspectives animal feeding, purification of products, and removing foreign DNA
Technical obstacles and living cells.
To have a fully incorporated use of microbes in food, there are some The safety of the foods must also be considered for each different
technical difficulties that must be overcome. First, one of the main species. There has already been extensive investigation into some of
nutritional drawbacks is the high content of nucleic acids—namely RNA the main target species that have confirmed their food safety both for
content. Ingestion of excessive quantities of nucleic acids particularly fermentation, ingredient production and SCP use. Special attention
purines, increases the quantity of uric acid in the body which is a risk must be paid to possible contamination in the process and to the
factor for gout and renal calculi as well as a strong risk factor for potential production of endo and exotoxins that cause allergic and
Metabolic Syndrome and cardiovascular disease112. This can be partially adverse reactions when ingested. Some toxins may be removed by
mitigated through processing methods, including heating and pur- simple heat or chemical treatments. However, through stringent strain
ification as employed by current single-cell protein manufacturers113,114. selection116, strain engineering117 and correct fermentation technolo-
In the future, it would be possible to envisage an inducible method gies, contamination and toxin production can be prevented or
engineered into microbes to self-purify excess nucleic acids. eliminated.
Consumer acceptance potential to revolutionise current food systems. This microbial food
One of the largest challenges of deploying single-cell proteins and revolution could be key in designing future-proof strategies to face the
genetically engineered microorganisms in food is consumer accep- health and environmental challenges of the future.
tance. Genetic modification is still under strict regulations, which differ
between countries with some being particularly strict on introducing References
food with modified genetic information. Moreover, a large percentage 1. Rockström, J., Edenhofer, O., Gaertner, J. & DeClerck, F. Planet-
of people still do not accept the idea of eating genetically modified proofing the global food system. Nat. Food 1, 3–5 (2020).
materials. With the increasing awareness of improving the ecological 2. Change, I. C. Land: An IPCC Special Report on Climate Change.
aspect of diets118, this attitude might be changing as seen with the Desertification, Land Degradation, Sustainable Land Management,
popularity with lab-grown meats and some synthetic meat and milk Food Security, and Greenhouse Gas Fluxes in Terrestrial Ecosys-
alternatives; however, these products are still uncommon in a com- tems 1–864 (IPCC, 2019).
mercial setting and therefore not incorporated in the average 3. Sun, Z. et al. Dietary change in high-income nations alone can
household’s diet. lead to substantial double climate dividend. Nat. Food 3,
To promote consumption, it is thus crucial to take the preparation 29–37 (2022).
and cultural context of microbial foods into account. Education and 4. Lv, X. et al. Synthetic biology for future food: research progress
marketing can help counteract unfamiliarity and lack of consumption and future directions. Future. Foods 3, 100025 (2021).
experience119. In addition, the design of microbial foods should con- 5. Choi, K. R., Yu, H. E. & Lee, S. Y. Microbial food: microorganisms
sider the need to fulfil religious or cultural values, such as kosher or repurposed for our food. Micro. Biotechnol. 15, 18–25 (2022).
halal requirements120. 6. Humpenöder, F. et al. Projected environmental benefits of repla-
cing beef with microbial protein. Nature 605, 90–96 (2022).
Economic barriers 7. Järviö, N., Maljanen, N. L., Kobayashi, Y., Ryynänen, T. & Tuomisto,
A large problem of deploying SCP is the capital expenditure needed to H. L. An attributional life cycle assessment of microbial protein
expand the technologies and market the new food source. Main- production: a case study on using hydrogen-oxidizing bacteria.
tenance costs and substrate usage also limit profitability. Because of Sci. Total Environ. 776, 145764 (2021).
the costs incurred for prototype development, one of the initial SCP 8. Javourez, U., O’Donohue, M. & Hamelin, L. Waste-to-nutrition: a
projects by Imperial Chemical Industries (ICI) was abandoned when it review of current and emerging conversion pathways. Biotechnol.
failed to compete with cheap agriculture, especially with modified Adv. 53, 107857 (2021).
soybeans10. However, more recent technologies seem to suggest that 9. Gao, R. et al. Enhanced lipid production by Yarrowia lipolytica
building a plant for growing microbes could now be economically cultured with synthetic and waste-derived high-content volatile
feasible121, which is facilitated by the optimisation of the growing fatty acids under alkaline conditions. Biotechnol. Biofuels 13,
conditions122, advanced fermentation technologies123, and higher 1–16 (2020).
yields achieved by engineered microbes100. Another economic barrier 10. Linder, T. Making the case for edible microorganisms as an inte-
for commercialisation is the lengthy and expensive process associated gral part of a more sustainable and resilient food production
with obtaining the necessary regulatory and safety approvals. system. Food Secur. 11, 265–278 (2019).
Although dependent on price, variety and transportation, the 11. Ravindra, P. Value-added food:: single cell protein. Biotechnol.
employment of waste streams also has the potential to lower the Adv. 18, 459–479 (2000).
process cost and simultaneously increase sustainability10. However, 12. Sharif, M. et al. Single cell protein: Sources, mechanism of pro-
this is harder to introduce to the market as it is not fully understood duction, nutritional value and its uses in aquaculture nutrition.
whether the nutritional qualities of the product would be affected. Aquaculture 531, 735885 (2021).
13. Marco, M. L. et al. Health benefits of fermented foods: microbiota
Conclusion and beyond. Curr. Opin. Biotechnol. 44, 94–102 (2017).
Taken together all the information discussed above, there is an 14. Pan, M. & Barrangou, R. Combining omics technologies with
obvious interest in developing more microbial-based foods and CRISPR-based genome editing to study food microbes. Curr.
ingredients, as seen by the increased number of related academic Opin. Biotechnol. 61, 198–208 (2020).
publications, conferences, companies and commercial products. This 15. Palla, M., Cristani, C., Giovannetti, M. & Agnolucci, M. Identifica-
is in part encouraged by the consumer demand for healthier and more tion and characterization of lactic acid bacteria and yeasts of PDO
sustainable foods. Tuscan bread sourdough by culture dependent and independent
Synthetic biology and microbial strain engineering broaden the methods. Int. J. Food Microbiol. 250, 19–26 (2017).
horizons of microbial foods that can be designed, enabling the 16. Steensels, J., Meersman, E., Snoek, T., Saels, V. & Verstrepen, K. J.
creation of desired nutritional profiles, aroma compounds, flavours Large-scale selection and breeding to generate industrial yeasts
and textures, all of which can build towards personalised nutrition with superior aroma production. Appl Environ. Microbiol. 80,
(Fig. 3). To translate this technological capability into sustainable 6965–6975 (2014).
commercial products, the public perception of microbial foods must 17. Marullo, P. & Dubourdieu, D. Yeast selection for wine flavor
continue to change and the legislation must facilitate the imple- modulation. in Managing Wine Quality (ed. Reynolds, A. G.)
mentation of these novel processes while maintaining high safety 371–426 (Elsevier, 2022). https://www.sciencedirect.com/book/
standards. The expansion and normalisation of microbial foods will 9780081020654/managing-wine-quality.
increase production volumes, decreasing costs and optimising the 18. Tamang, J. P., Shin, D.-H. H., Jung, S.-J. J. & Chae, S.-W. W. Func-
efficiency of the technology. Reduced costs can then aid the devel- tional properties of microorganisms in fermented foods. Front.
opment of microbial processes in less developed areas of the planet, Microbiol. 7, 578 (2016).
which often need to improve nutrition. Looking at the future, engi- 19. Sen, T., Barrow, C. J. & Deshmukh, S. K. Microbial pigments in the
neered microbes are expected to play a role in delivering food where food industry—challenges and the way forward. Front. Nutr. 6,
traditionally inaccessible, such as in disaster relief, deserts or even in 7 (2019).
space124,125. 20. Wang, Y., Liu, L., Jin, Z. & Zhang, D. Microbial cell factories for
In conclusion, if there is continued innovation and microbial green production of vitamins. Front. Bioeng. Biotechnol. 9,
foods are designed with sustainability and ethics in mind, they have the 473 (2021).
21. Yuan, S.-F. F. & Alper, H. S. Metabolic engineering of microbial cell 43. Andreasen, A. S. et al. Effects of Lactobacillus acidophilus NCFM
factories for production of nutraceuticals. Micro. Cell Fact. 18, on insulin sensitivity and the systemic inflammatory response in
1–11 (2019). human subjects. Br. J. Nutr. 104, 1831–1838 (2010).
22. Banks, M., Johnson, R., Giver, L., Bryant, G. & Guo, M. Industrial 44. de Angelis, M. et al. Use of sourdough lactobacilli and oat fibre to
production of microbial protein products. Curr. Opin. Biotechnol. decrease the glycaemic index of white wheat bread. Br. J. Nutr. 98,
75, 102707 (2022). 1196–1205 (2007).
23. Jones, S. W., Karpol, A., Friedman, S., Maru, B. T. & Tracy, B. P. 45. Shetty, P. H. & Jespersen, L. Saccharomyces cerevisiae and lactic
Recent advances in single cell protein use as a feed ingredient in acid bacteria as potential mycotoxin decontaminating agents.
aquaculture. Curr. Opin. Biotechnol. 61, 189–197 (2020). Trends Food Sci. Technol. 17, 48–55 (2006).
24. Shurson, G. C. Yeast and yeast derivatives in feed additives and 46. Nkhata, S. G., Ayua, E., Kamau, E. H. & Shingiro, J.-B. Fermentation
ingredients: Sources, characteristics, animal responses, and and germination improve nutritional value of cereals and legumes
quantification methods. Anim. Feed Sci. Technol. 235, through activation of endogenous enzymes. Food Sci. Nutr. 6,
60–76 (2018). 2446–2458 (2018).
25. Helmy, M., Elhalis, H., Yan, L., Chow, Y. & Selvarajoo, K. Perspec- 47. Fang, H. et al. Metabolic engineering of Escherichia coli for de
tive: multi-omics and machine learning help unleash the alter- novo biosynthesis of vitamin B12. Nat. Commun. 9, 1–12 (2018).
native food potential of microalgae. Adv. Nutr. 14, 1–11 (2022). 48. Shen, B. et al. Fermentative production of vitamin E tocotrienols in
26. Reyes, T. F., Chen, Y., Fraser, R. Z., Chan, T. & Li, X. Assessment of Saccharomyces cerevisiae under cold-shock-triggered tempera-
the potential allergenicity and toxicity of Pichia proteins in a novel ture control. Nat. Commun. 11, 1–14 (2020).
leghemoglobin preparation. Regul. Toxicol. Pharmacol. 119, 49. Maintz, L. & Novak, N. Histamine and histamine intolerance. Am. J.
104817 (2021). Clin. Nutr. 85, 1185–1196 (2007).
27. Xue, Z. et al. Production of omega-3 eicosapentaenoic acid by 50. Barbieri, F., Montanari, C., Gardini, F. & Tabanelli, G. Biogenic
metabolic engineering of Yarrowia lipolytica. Nat. Biotechnol. 31, amine production by lactic acid bacteria: a review. Foods 8,
734–740 (2013). 17 (2019).
28. Yan, J. et al. Engineering Yarrowia lipolytica to simultaneously 51. Li, B. & Lu, S. The importance of amine-degrading enzymes on the
produce lipase and single cell protein from agro-industrial wastes biogenic amine degradation in fermented foods: a review. Process
for feed. Sci. Rep. 8, 1–10 (2018). Biochem. 99, 331–339 (2020).
29. Gleizer, S. et al. Conversion of Escherichia coli to generate all 52. Marco, M. L. et al. The international scientific association for
biomass carbon from CO2. Cell 179, 1255–1263.e12 (2019). probiotics and prebiotics (ISAPP) consensus statement on fer-
30. Legras, J.-L., Merdinoglu, D., Cornuet, J.-M. & Karst, F. Bread, beer mented foods. Nat. Rev. Gastroenterol. Hepatol. 18,
and wine: Saccharomyces cerevisiae diversity reflects human 196–208 (2021).
history. Mol. Ecol. 16, 2091–2102 (2007). 53. Jach, M. E., Serefko, A., Ziaja, M. & Kieliszek, M. Yeast protein as an
31. Dudley, R. Ethanol, fruit ripening, and the historical origins of easily accessible food source. Metabolites 12, 63 (2022).
human alcoholism in primate frugivory. Integr. Comp. Biol. 44, 54. Yamada, E. A. & Sgarbieri, V. C. Yeast (Saccharomyces cerevisiae)
315–323 (2004). protein concentrate: preparation, chemical composition, and
32. Tamang, J. P. et al. Fermented foods in a global age: East meets nutritional and functional properties. J. Agric Food Chem. 53,
West. Compr. Rev. Food Sci. Food Saf. 19, 184–217 (2020). 3931–3936 (2005).
33. Taylor, B. C. et al. Consumption of fermented foods is associated 55. Wastyk, H. C. et al. Gut-microbiota-targeted diets modulate
with systematic differences in the gut microbiome and metabo- human immune status. Cell 184, 4137–4153 (2021).
lome. mSystems 5, e00901–e00919 (2020). 56. Moreira, J. B. et al. Microalgae polysaccharides: an alternative
34. Kim, J. & Adhikari, K. Current trends in kombucha: marketing source for food production and sustainable agriculture. Poly-
perspectives and the need for improved sensory research. Bev- saccharides 3, 441–457 (2022).
erages 6, 15 (2020). 57. McFarlin, B. K., Carpenter, K. C., Davidson, T. & McFarlin, M. A.
35. He, J., Evans, N. M., Liu, H. & Shao, S. A review of research on plant- Baker’s yeast beta glucan supplementation increases salivary iga
based meat alternatives: driving forces, history, manufacturing, and decreases cold/flu symptomatic days after intense exercise. J.
and consumer attitudes. Compr. Rev. Food Sci. Food Saf. 19, Diet. 10, 171–183 (2013).
2639–2656 (2020). 58. Cuskin, F. et al. Human gut Bacteroidetes can utilize yeast mannan
36. Singh, S., Yap, W. S., Ge, X. Y., Min, V. L. X. & Choudhury, D. through a selfish mechanism. Nature 517, 165–169 (2015).
Cultured meat production fuelled by fermentation. Trends Food 59. Ratledge, C. Fatty acid biosynthesis in microorganisms being used
Sci. Technol. 120, 48–58 (2022). for single cell oil production. Biochimie 86, 807–815 (2004).
37. Şanlier, N., Gökcen, B. B. & Sezgin, A. C. Health benefits of fer- 60. Jach, M. E., Serefko, A., Ziaja, M. & Kieliszek, M. Yeast protein as an
mented foods. Crit. Rev. Food Sci. Nutr. 59, 506–527 (2017). easily accessible food source. Metabolites 12, 63 (2022).
38. Clemente, J. C., Ursell, L. K., Parfrey, L. W. & Knight, R. The impact 61. Ritala, A., Häkkinen, S. T., Toivari, M. & Wiebe, M. G. Single cell
of the gut microbiota on human health: an integrative view. Cell protein—state-of-the-art, industrial landscape and patents
148, 1258–1270 (2012). 2001–2016. Front. Microbiol. 8, 2009 (2017).
39. Suez, J., Zmora, N., Segal, E. & Elinav, E. The pros, cons, and many 62. Arendt, E. K., Moroni, A. & Zannini, E. Medical nutrition therapy: use
unknowns of probiotics. Nat. Med. 25, 716–729 (2019). of sourdough lactic acid bacteria as a cell factory for delivering
40. Wastyk, H. C. et al. Gut-microbiota-targeted diets modulate functional biomolecules and food ingredients in gluten free
human immune status. Cell 184, 4137–4153 (2021). bread. Micro. Cell Fact. 10, 1–9 (2011).
41. Bergqvist, S. W., Sandberg, A.-S., Carlsson, N.-G. & Andlid, T. 63. Waters, D. M., Mauch, A., Coffey, A., Arendt, E. K. & Zannini, E.
Improved iron solubility in carrot juice fermented by homo-and Lactic acid bacteria as a cell factory for the delivery of functional
hetero-fermentative lactic acid bacteria. Food Microbiol. 22, biomolecules and ingredients in cereal-based beverages: a
53–61 (2005). review. Crit. Rev. Food Sci. Nutr. 55, 503–520 (2015).
42. Osman, M. A. Changes in sorghum enzyme inhibitors, phytic acid, 64. Leroy, F. & de Vuyst, L. Lactic acid bacteria as functional starter
tannins and in vitro protein digestibility occurring during Khamir cultures for the food fermentation industry. Trends Food Sci.
(local bread) fermentation. Food Chem. 88, 129–134 (2004). Technol. 15, 67–78 (2004).
65. Denby, C. M. et al. Industrial brewing yeast engineered for the 86. Duale, A., Singh, P. & Al Khodor, S. Breast milk: a meal worth
production of primary flavor determinants in hopped beer. Nat. having. Front Nutr. 8, 800927 (2022).
Commun. 9, 1–10 (2018). 87. Lu, M., Mosleh, I. & Abbaspourrad, A. Engineered microbial routes
66. Ledesma-Amaro, R. & Nicaud, J. M. Metabolic engineering for for human milk oligosaccharides synthesis. ACS Synth. Biol. 10,
expanding the substrate range of Yarrowia lipolytica. Trends Bio- 923–938 (2021).
technol. 34, 798–809 (2016). 88. Bhutada, G. et al. Production of human milk fat substitute by
67. Malav, A., Meena, S., Sharma, M., Sharma, M. & Dube, P. A critical engineered strains of Yarrowia lipolytica. Metab. Eng. Commun. 14,
review on single cell protein production using different sub- e00192 (2022).
strates. Int. J. Dev. Res. 7, 16682–16687 (2017). 89. Braegger, C. et al. Supplementation of infant formula with pro-
68. Abram, F. Systems-based approaches to unravel multi-species biotics and/or prebiotics: a systematic review and comment by
microbial community functioning. Comput Struct. Biotechnol. J. the ESPGHAN committee on nutrition. J. Pediatr. Gastroenterol.
13, 24–32 (2015). Nutr. 52, 238–250 (2011).
69. Sabra, W., Dietz, D., Tjahjasari, D. & Zeng, A. P. Biosystems analysis 90. Rupa, P. & Mine, Y. Structural and immunological characterization
and engineering of microbial consortia for industrial biotechnol- of recombinant ovomucoid expressed in Escherichia coli. Bio-
ogy. Eng. Life Sci. 10, 407–421 (2010). technol. Lett. 25, 427–433 (2003).
70. McCarty, N. & Ledesma-Amaro, R. Synthetic biology tools to 91. Upadhyay, V., Singh, A. & Panda, A. K. Purification of recombinant
engineer microbial communities for biotechnology. Trends Bio- ovalbumin from inclusion bodies of Escherichia coli. Protein Expr.
technol. 37, 181–197 (2019). Purif. 117, 52–58 (2016).
71. Det-Udom, R. et al. Towards semi-synthetic microbial commu- 92. Järviö, N. et al. Ovalbumin production using Trichoderma reesei
nities: enhancing soy sauce fermentation properties in B. subtilis culture and low-carbon energy could mitigate the environmental
co-cultures. Micro. Cell Fact. 18, 1–8 (2019). impacts of chicken-egg-derived ovalbumin. Nat. Food 2,
72. Li, J. et al. Cooperation of lactic acid bacteria regulated by the AI- 1005–1013 (2021). 2022 2:12.
2/LuxS system involve in the biopreservation of refrigerated 93. Aro, N. et al. Production of bovine beta-lactoglobulin and hen egg
shrimp. Food Res. Int. 120, 679–687 (2019). ovalbumin by Trichoderma reesei using precision fermentation
73. Jenkins, G. in SCP—The BP Protein Process. Resources and Appli- technology and testing of their techno-functional properties. Food
cations of Biotechnology (ed. Greenshields, R.) 141–149 (Springer, Res. Int. 163, 112131 (2023).
1988). https://link.springer.com/book/10.1007/978-1-349- 94. Dunn-Coleman, N. S. et al. Commercial levels of chymosin pro-
09574-2. duction by Aspergillus. BioTechnology 9, 976–981 (1991).
74. Hamdan, I. & Senez, J. Protein (SCP) production in the twenty-first 95. Giec, A. & Skupin, J. Single cell protein as food and feed. Food/
century. in Biotechnology: Economic and Social Aspects: Issues for Nahr. 32, 219–229 (1988).
Developing Countries. (eds DaSilva, E. J. & Ratledge, C.) 142–164 96. Kim, S. W. et al. Meeting global feed protein demand: challenge,
(Cambridge University Press, 1992). https://www.cambridge.org/ opportunity, and strategy. Annu. Rev. Anim. Biosci. 7,
core/books/biotechnology-economic-and-social-aspects/ 221–243 (2019).
1EE6FBE4E3C1028E2CF7D0C47640D7BD. 97. Chaucheyras-Durand, F. & Durand, H. Probiotics in animal nutrition
75. Ritala, A., Häkkinen, S. T., Toivari, M. & Wiebe, M. G. Single cell and health. Benef. Microbes 1, 3–9 (2010).
protein-state-of-the-art, industrial landscape and patents 2001- 98. Rollo, A. et al. Live microbial feed supplement in aquaculture for
2016. Front. Microbiol. 8, 2009 (2017). improvement of stress tolerance. Fish. Physiol. Biochem 32,
76. Finnigan, T. J. A. et al. Mycoprotein: the future of nutritious non- 167–177 (2006).
meat protein, a symposium review. Curr. Dev. Nutr. 3, 99. Dawson, K. A., Newman, K. E. & Boling, J. A. Effects of microbial
nzz021 (2019). supplements containing yeast and lactobacilli on roughage-fed
77. Janssen, M., Wijffels, R. H. & Barbosa, M. J. Microalgae based ruminal microbial activities. J. Anim. Sci. 68, 3392–3398
production of single-cell protein. Curr. Opin. Biotechnol. 75, (1990).
102705 (2022). 100. Balabanova, L. et al. Engineered fungus Thermothelomyces
78. Balagurunathan, B., Ling, H., Choi, W. J. & Chang, M. W. Potential thermophilus producing plant storage proteins. J. Fungi 8,
use of microbial engineering in single-cell protein production. 119 (2022).
Curr. Opin. Biotechnol. 76, 102740 (2022). 101. Xie, D., Jackson, E. N. & Zhu, Q. Sustainable source of omega-3
79. Zha, X. et al. Bioconversion of wastewater to single cell protein by eicosapentaenoic acid from metabolically engineered Yarrowia
methanotrophic bacteria. Bioresour. Technol. 320, 124351 (2021). lipolytica: from fundamental research to commercial production.
80. Whittaker, J. A., Johnson, R. I., Finnigan, T. J. A. A., Avery, S. V. & Appl. Microbiol. Biotechnol. 99, 1599–1610 (2015).
Dyer, P. S. The biotechnology of quorn mycoprotein: past, present 102. Revuelta, J. L. et al. Bioproduction of riboflavin: a bright yellow
and future challenges. in Grand Challenges in Fungal Bio- history. J. Ind. Microbiol. Biotechnol. 44, 659–665 (2017).
technology (ed. Nevalainen, H.) 59–79 (Springer, 2020). 103. Hanlon, P. & Sewalt, V. GEMs: genetically engineered micro-
81. Vegetarian & Vegan Products, Meat Free Recipes & News | Quorn. organisms and the regulatory oversight of their uses in modern
https://www.quorn.co.uk/. food production. Crit. Rev. Food Sci. Nutr. 61, 959–970 (2020).
82. Zhao, X. R., Choi, K. R. & Lee, S. Y. Metabolic engineering of 104. Ledesma-Amaro, R., Jiménez, A., Santos, M. A. & Revuelta, J. L.
Escherichia coli for secretory production of free haem. Nat. Catal. Biotechnological production of feed nucleotides by microbial
1, 720–728 (2018). 2018 1:9. strain improvement. Process Biochem. 48, 1263–1270 (2013).
83. Nokelainen, M. et al. High-level production of human type I col- 105. Moon, H.-J., Jeya, M., Kim, I.-W. & Lee, J.-K. Biotechnological pro-
lagen in the yeast Pichia pastoris. Yeast 18, 797–806 (2001). duction of erythritol and its applications. Appl. Microbiol. Bio-
84. Williams, K. E. & Olsen, D. R. Gelatin expression from an engi- technol. 86, 1017–1025 (2010).
neered Saccharomyces cerevisiae CUP1 promoter in Pichia pas- 106. Mohamad, N. L., Mustapa Kamal, S. M. & Mokhtar, M. N. Xylitol
toris. Yeast 38, 382–387 (2021). biological production: a review of recent studies. Food Rev. Int. 31,
85. Ledesma-Amaro, R. Microbial oils: a customizable feedstock 74–89 (2015).
through metabolic engineering. Eur. J. Lipid Sci. Technol. 117, 107. Xu, Y. et al. De novo biosynthesis of rubusoside and rebaudiosides
141–144 (2015). in engineered yeasts. Nat. Commun. 13, 1–12 (2022).
108. Celińska, E. et al. Genetic engineering of Ehrlich pathway mod- 123. Linder, T. Edible microorganisms—an overlooked technology
ulates production of higher alcohols in engineered Yarrowia lipo- option to counteract agricultural expansion. Front. Sustain Food
lytica. FEMS Yeast Res. 19, foy122 (2019). Syst. 3, 32 (2019).
109. Li, J. et al. Simultaneous improvement of limonene production and 124. Menezes, A. A., Montague, M. G., Cumbers, J., Hogan, J. A. & Arkin,
tolerance in Yarrowia lipolytica through tolerance engineering and A. P. Grand challenges in space synthetic biology. J. R. Soc.
evolutionary engineering. ACS Synth. Biol. 10, 884–896 (2021). Interface 12, 20150803 (2015).
110. Toogood, H. S. et al. Enzymatic menthol production: one-pot 125. García Martínez, J. B. et al. Potential of microbial protein from
approach using engineered Escherichia coli. ACS Synth. Biol. 4, hydrogen for preventing mass starvation in catastrophic scenar-
1112–1123 (2015). ios. Sustain Prod. Consum. 25, 234–247 (2021).
111. Ledesma-Amaro, R. & Nicaud, J.-M. Yarrowia lipolytica as a bio-
technological chassis to produce usual and unusual fatty acids. Acknowledgements
Prog. Lipid Res. 61, 40–50 (2016). R.L.-A. received funding from BBSRC (BB/R01602X/1, BB/T013176/1, BB/
112. de Oliveira, E. P. & Burini, R. C. High plasma uric acid concentra- T011408/1–19-ERACoBioTech- 33 SyCoLim), British Council 527429894,
tion: causes and consequences. Diabetol. Metab. Syndr. 4, Newton Advanced Fellowship (NAF\R1\201187), Yeast4Bio Cost Action
1–7 (2012). 18229, European Research Council (ERC) (DEUSBIO–949080) and the
113. O’Donnell, K., Cigelnik, E. & Casper, H. H. Molecular phylogenetic, Bio-based Industries Joint (PERFECOAT- 101022370) under the European
morphological, and mycotoxin data support reidentification of the Union’s Horizon 2020 research and innovation programme.
quorn mycoprotein fungus as Fusarium venenatum. Fungal Genet.
Biol. 23, 57–67 (1998). Author contributions
114. Nasseri, A. T., Rasoul-Amini, S., Morowvat, M. H. & Ghasemi, Y. The article was ideated by R.L.A. and A.E.G. A.E.G. wrote the first draft
Single cell protein: production and process. Am. J. Food Technol. with inputs from R.L.A. R.L.A. supervised, edited and polished the article.
6, 103–116 (2011).
115. Hansen, E. H. et al. De novo biosynthesis of vanillin in fission yeast Competing interests
(Schizosaccharomyces pombe) and baker’s yeast (Saccharomyces The authors declare no competing interests.
cerevisiae). Appl. Environ. Microbiol. 75, 2765–2774 (2009).
116. Kovac, J., den Bakker, H., Carroll, L. M. & Wiedmann, M. Precision Additional information
food safety: a systems approach to food safety facilitated by Correspondence and requests for materials should be addressed to
genomics tools. TrAC Trends Anal. Chem. 96, 52–61 (2017). Rodrigo Ledesma-Amaro.
117. Liu, W. et al. A dual-plasmid CRISPR/Cas system for mycotoxin
elimination in polykaryotic industrial fungi. ACS Synth. Biol. 9, Reprints and permissions information is available at
2087–2095 (2020). http://www.nature.com/reprints
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Older consumers’ readiness to accept alternative, more sustain- Publisher’s note Springer Nature remains neutral with regard to jur-
able protein sources in the European Union. Nutrients 11, isdictional claims in published maps and institutional affiliations.
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119. Onwezen, M. C., Bouwman, E. P., Reinders, M. J. & Dagevos, H. A
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