How could synthetic biology change the food we eat? Microorganisms

Written by Lewis Wallis, Edited by Natasha Barrow and Aidan Kendrick.

With recent progress in developing tools that can manipulate genetic material, the concept of ‘Synthetic Biology’ has rapidly evolved and applies the principles of engineering to the world of biotechnology. Early research focussed on the alteration of simple pathways, but now the creation of entirely synthetic microorganisms is possible. Genetic modification has often been a controversial issue in the context of our food systems, but employing new technologies which introduce beneficial properties to our food may help to pave a new way forward for the debate in this area.

What is synthetic biology?

The discipline of Synthetic Biology (SynBio) aims to drive the design, manufacture, and modification of biological systems, expanding the capacity of what living cells are capable of. By combining elements of genetic engineering and computer modelling, SynBio uses techniques such as Genetic Modification (GM) and CRISPR to strategically enhance the capabilities of genetic material and improve its resulting characteristics.

What tools can we use to modify DNA?

Genetic information can be combined with a “vector” to produce what is known as recombinant DNA, which can be directly inserted into cells.

**Taken from:** https://www.addgene.org/mol-bio-reference/

As you might expect, gene insertion is the addition of DNA building blocks (nucleotides) into a DNA sequence, therefore introducing something new to the genetic code. On the other hand, gene deletion is an alteration which leads to the removal of nucleotides from the sequence. An important tool used by researchers for the insertion or deletion of genes is CRISPR, which can customise the DNA of animals, plants and microorganisms.

How can SynBio be applied to the foods we eat?

Biological organisms are put to use in a number of ways, with the food we eat being no exception. It can be seen with microbial cultures used in fermentation to produce cheese and yogurt, fungi for QuornTM or yeast for bread and beer production. These examples highlight the incredibly important role of microorganisms within our food system. Further innovation in this area is also taking place through the development of alternative proteins that are more sustainable, with more examples that can be found here.

Utilising microorganisms derived from the SynBio approach has potential within our food systems and could be available on the market in the next decade, with applications across the spectrum of the agri-food landscape including for foods, additives, feed materials and plant protection products. It is no surprise then that SynBio is on the radar of the European Food Safety Authority (EFSA) who recently published a Scientific Opinion covering applications for microorganisms. It highlighted the important features that should be considered to ensure the risks are properly understood and managed. But what are the applications for our food system? And where are the potential growth opportunities in this area?

Applications using SynBio for food products and supplements

Soy sauce

As part of the fermentation process, specific bacteria are used to break down substances. Soy sauce is traditionally made in a fermentation process by mixing soybeans and grain with mould cultures (e.g. Aspergillus oryzae). To improve the quality of the soy sauce produced, a genetic modification technique can be used to increase the quantity of compounds that produce flavour in the final product [1]. Adding this new genetic component also increases the microorganism’s genetic stability and could improve the efficiency of the overall process.

Yogurt, cheese & kefir

Lactic acid bacteria (LAB) are of particular interest in the world of food as they are used in the fermentation of yogurt, cheese and kefir; after being processed by our digestive system, they can have a probiotic effect and contribute to the natural balance of bacteria in the gut [2]. These microbial processes can also be put to use in industry for the production of Vitamin B2 which, although is often naturally found in animal products, can be sold as a supplement or added to fortify foods. An example of SynBio here comes from a study that used CRISPR to manipulate a bacterial strain and increase its capacity to produce Vitamin B2 [3]. As a result, using this strain for food fermentation could improve the nutrient profile of fermented products. A novel industry method could also be adapted from further research in this area leading to a more efficient industry process for vitamin production, with potential uses in food supplements or feed additives.

Probiotics

Lactococcus lactis is another commonly used culture in the dairy fermentation industry. The strain can be genetically engineered to include specific factors that increase the strength by which it can attach to the gastrointestinal tract [4]. Of concern is the ability of some ‘probiotic’ strains to remain in the gut for a significant period in order to exhibit a beneficial effect. In this case, increasing the strength of attachment may enhance the probiotic effect observed when using this strain.

Utilising SynBio for the production of feed materials and feed additives

Food enzymes

Enzymes are biological proteins that are used in the food and drink industry and can help with reducing alcohol concentration in beer or assist with maintaining the texture of bread. Pichia pastoris is a type of yeast commonly used for the manufacture of these industrial enzymes. Its growth relies on the use of organic feedstock that could otherwise be used for food or animal feed. Targeted insertion and deletion of genes can help to alter the metabolism of the yeast and transform it to be capable of growth using CO2 [5]. Applications of this modified strain then could include the sustainable production of biomass for food and feed purposes by transforming CO2 into organic matter.

Colouring foods as feed additives

Derived from algae, the biomass product of Spirulina is often used in the food industry to colour products blue. Using a similar method of gene insertion on the Spirulina strain, oral delivery of the manufactured product can help to prevent Campylobacter infection and was predicted to do so when consumed by animals as a feed additive [6].

What is the future of synthetic biology in food?

A synthetic biology approach can not only produce the same results as traditional genetic modification technology, but also create new-to-nature products. The use of components such as xenobiotic nucleic acids (XNAs) has been highlighted as a

tool that may be used for synthetic biology approaches in the future. XNAs are alternatives to natural nucleic acids that we find in our DNA and they have potential applications for microorganisms, for example, by increasing the antimicrobial activity of antibiotics used in the food system. However, these components could be of concern considering their limited stability and ability to degrade into potentially harmful metabolites that could trigger allergenicity [7]. As identified by EFSA, it would therefore be important to ensure that any products derived from XNAs are properly assessed regarding their safety to identify any harmful effects. Despite developments in the area, this novel approach is still at an early research stage and is not expected to see applications for food any time soon.

It is much more likely that within the next decade we will see further research build to support the current applications for food like GM and CRISPR. It is of great importance to test whether any resulting microorganisms have the potential to be pathogenic, toxic, allergenic or negatively affect our gut bacteria. When they are at the appropriate stage and ready for development, they will need to undergo the relevant pre-market authorisation before being used in our foods. This will be key to building consumer confidence in the applications for synthetic biology and continue to ensure the safety of the food we eat.