GMOs and Flavor Production – Are Flavors Produced Using Genetically Modified Microorganisms Natural?

Updates and discussions in Europe

Microorganisms have been used for fermenting food and beverage products for thousands of years. It was not until the nineteenth century that the microorganisms responsible for the fermentation of many food products such as cheese were identified and described. As biochemical knowledge advanced the mechanisms of fermentation became better understood and mapped out. Specifics enzymes were isolated and their activities in the fermentation processes elucidated in detail. With the advent of genetic engineering, new tools became available to modify microorganisms in order to optimize functions such as enzyme production. Genetic modifications greatly benefitted some industries such as cheesemaking, where GMM play the primary enzymatic roll in fermentation of milk into cheese in many parts of the world.

The science of genetic engineering opened lead to opportunity to improve product, but also lead to greater scrutiny of the technology to ensure consumer safety. Laws and regulations were implemented address potential safety concerns around food that leveraged genetic engineering. For example, before a food containing GMOs is released into the marketplace, it must undergo significant review to demonstrate it is safe for consumption. The safety review of GMOs is by all accounts very robust and rigorous. There are no verified documents of negative health effects directly related to genetic modification of food.

Nevertheless, there have been calls for the consumer-facing disclosures on the GMO foods. As such regulations like the EU regulation on traceable and labelling GMOs (regulation (EC) No 1830/2003) or the USDA bioengineered disclosure food disclosure standard (7 CFR 66) require food containing GMO to be labeled as such. Food labels now clearly indicate which foods consist of GMOs. Such labeling may cause confusion for consumers, however, since they are not linked to any health concern or health benefit, but rather, are purely informational.

The GMO/Bioengineered food labelling requirements apply to foods that contain GMOs, but what is the impact of these labeling requirements on foods produced using GMM? If the food was produced using GMM but does not contain any of the modified genetic materials, for the most part there is no disclosure required. So, if a microorganism is genetically modified to produce a flavor like valencene the flavor itself does not contain genetic material, so it would not be labeled or identified as GMO under US or EU requirements. In other words, food produced using GMM do not require GMO/bioengineered label disclosures, if there is no significant amount of the genetic material from the GMM present in the food. A common analogy is linked to meat production. The meat from a GMO animal must be labeled as GM. If the animal itself is not GMO, but is fed GMO feed, the meat is not GMO since it does not contain any of the genetic material from the feed. So, flavors produced using GMM, but not containing the GMM are not labeled as bioengineered or GMO.

Even though they are not themselves considered a genetically modified food, are flavors produced from fermentation using GMM or enzymes derived from GMM natural? There are very specific regulations regarding the use of the term natural as is applies to flavors. In the EU this definition is found in regulation (EC) 1334/2008. In summary, the regulations states that natural flavors must be identified in nature, obtained from vegetable, animal, or microbiological material, and produced using traditional physical, enzymatic, or microbiological processes. So, vanillin produced from the fermentation of sugars by GMM meets the first two criteria indicated above. Vanillin is found in nature, and if it is produced from sugars, then it is produced from vegetable material. But is it produced by a traditional enzymatic or microbiological method. Fermentation by microorganism is a traditional method for producing food, so the regulation seems to be clear that vanillin produced using GMM is natural.

There have been some recent concerns over the use GMMs and natural labeling, however. Firstly, since the EU requires that natural flavors be produced from “appropriate physical, enzymatic or microbiological processes… by one or more traditional food preparation processes” the flavor manufacturing method must be considered traditional for the flavor to be labelled natural. Although fermentation is a certainly a traditional food manufacturing method, some have argued that fermentation with GMM is not traditional. Since the European Food Safety Authority (EFSA) has not yet responded to this assessment, some insight on the likely EFSA approach may surmised based on their opinion on modern genetic modification methods.

The EU definition of GMO (Directive 2001/18/EC) requires GMO labeling only where new genes are introduced into an organism. The regulation exempts the definition of GMO from those organisms produced through mutagenesis (Directive 2001/18/EC Art 3). Mutagenesis refers to the changing or manipulation of existing genes in an organism (as opposed to transgenesis with involves the introduction of new genes into an organism). Mutagenesis has been used since the 1920s when it was discovered certain types of radiation, such as UV radiation, can cause mutation in seeds. The EU concluded foods produced from such methods do not require a GMO label.

There have been some arguments within the EU, however, that modern mutagenic methods introduced after the implementation of Directive 2001/18/EC such as CRIPSR-Cas9, TALEN, or Zinc-Finger Nuclease (ZFN), should not fall within the mutagenesis exemption. In other words, there have been call within the EU to require GMO labeling on foods produced from these modern mutagenesis methods. Some groups have proposed the 2001 regulation did not consider the precision, efficiency, or speed of modern mutagenesis methods, and therefore these methods should result in GMO declarations on food. EFSA has so far rejected this argument. In fact, as recently as July 2024 EFSA asserted that not only is there no evidence modern mutagenic methods would introduce any signification safety concerns not already addressed under existing food safety and GMO regulations in the EU, but they likely are also safer than older genetic methods since they offer more precise control on the genetic modifications.

So, with respect to the use of GMMs in fermentation, it seems unlikely EFSA will change to the definition of natural flavors. The use of GMM or enzymes from GMM such as chymosin have been used in cheese-making since 1990, predating the EU GMO regulations by a more than a decade. Fermentation with GMM was well established when the EU natural flavor regulation was adopted. Additionally, no safety or health concerns have arisen with flavors produced using GMM. As with all regulations, however, one must continue to monitor and review to make all labels and declarations on flavors or other foods are clear and accurate. Public opinion, and consumer advocacy can influence labeling requirements and declarations even where no consumer health impact is known. We will continue to monitor the development in this other food regulations.