Fermentation-derived ingredients are already widely used across the nutraceutical industry: for example, many vitamins in supplements and fortified processed foods are produced through fermentation.
However, precision fermentation, a means of producing gene-edited microbes, yeast, or algae in lab-controlled environments to create specific functional ingredients, represents a major improvement in terms of efficiency, yield, and product quality.
Precision fermentation: A sustainable and scalable technology
The technique, which has been lauded for its sustainability credentials, has the potential to reduce the footprint of food production dramatically.
One study estimates that precision fermentation using methanol requires 1,700 times less land than the most efficient agricultural means of producing protein – soy grown in the US. This means it might use 138,000 and 157,000 times less land than the least efficient means: beef and lamb production.
Precision fermentation allows for scalable manufacture of virtually any ingredient, enabling companies to replace protein- and fat-rich foods – many of which are obtained from animal sources – with more sustainable alternatives.
It can also be used to produce bioactive compounds of interest to the nutraceutical industry.
Precision fermentation to produce riboflavin, resveratrol, and astaxanthin
One popular nutraceutical ingredient that can be produced using precision fermentation is riboflavin, or vitamin B2. Approved as a novel food by the European Food Safety Authority (EFSA) in 2014, it is produced by fermenting a genetically modified Bacillus subtilis strain.
Another is resveratrol. This polyphenol, which occurs naturally in grapes, peanuts, and berries, has antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective effects, and as such can protect against chronic diseases.
The Swiss biotech company Evolva uses precision fermentation to make its resveratrol – which has been approved by EFSA as a novel food, up to 500 mg/day. It can be used in multiple applications, including capsules, tablets, softgels, liquid shots, beverages, powder sticks, and chewing gum. The company has also developed a formulation that can be integrated into pet dietary supplements.
Astaxanthin, a carotenoid and pigment typically derived from algae, can also be produced via precision fermentation. Chinese supplier BGG and its subsidiary, Algae Health Sciences (AlgaeHealth), has novel food approval for both its supercritical and ethanol Haematococcus pluvialis extracts. The compound has potential benefits for brain, eye, immune, and skin health.
Novel foods process and precision fermentation-produced ingredients
A spokesman for EFSA explained the process by which precision fermentation-derived ingredients are regulated.
He told Vitafoods Insights: “The regulatory framework under which the product is assessed depends on the intended use (eg. novel food, additive, enzyme) but also on the presence or not of the [genetically modified microorganisms] GMM in the final product.
“In novel foods, the absence of viable cells and DNA of the GMM in the final product must be demonstrated. Otherwise, it would fall under the GMO regulatory framework.”
He said the agency had received “a series of applications related to precision fermentation”, using GMMs to produce food ingredients, food/feed additives, and food enzymes, among others.
Most of the ingredients he gave as examples “are human-identical milk oligosaccharides (HiMOs) intended to be used in food supplements, food for special medical purposes, total diet replacement for weight control”.
He explained: “Once EFSA carries out its assessment, the European Commission and EU Member State authorities decide whether to authorise the product or not, and the conditions of use.”
Risk assessments that have been finalised include:
- 2′-fucosyllactose (2’-FL) produced by a genetically modified strain (APC199) of Corynebacterium glutamicum ATCC 13032 (EFSA NDA Panel, 2022c);
- Lacto-N-tetraose (LNT) produced by genetically modified strains of Escherichia coli BL21 (DE3) (EFSA NDA Panel, 2020c);
- 2’-FL and lacto‐N‐neotetraose (LNnT) produced by genetically modified strains of E. coli K-12 DH1 (EFSA NDA Panel, 2022d);
- 2’-FL/difucosyllactose (DFL) mixture produced by a genetically modified strain of E. coli K-12 DH1 (EFSA NDA Panel, 2019a);
- LNT produced by genetically modified strains of E. coli K-12 DH1 (EFSA NDA Panel, 2019b) or E. coli BL21 (DE3) (EFSA NDA Panel, 2022e);
- Extension of use in food supplements for infants of 2’-FL/DFL mixture and LNT produced by genetically modified strains of E. coli K-12 DH1 (EFSA NDA Panel, 2022f);
- 3′‐sialyllactose (3′‐SL) sodium salts produced by genetically modified strains of E. coli K-12 DH1 (EFSA NDA Panel, 2020a) or E. coli BL21 (DE3) (EFSA NDA Panel, 2022a);
- 6′‐sialyllactose (6′‐SL) sodium salts produced by genetically modified strains of E. coli K-12 DH1 (EFSA NDA Panel, 2020b) or E. coli BL21 (DE3) (EFSA NDA Panel, 2022b), or by E. coli NEO6, a genetically modified strain of the same parental strain E. coli W (ATCC 9637) (EFSA NDA Panel, 2023a);
- 3-fucosyllactose (3-FL) produced by genetically modified strains of E. coli K-12 MG1655 (EFSA NDA Panel, 2021), E. coli BL21 (DE3) (EFSA NDA Panel, 2022g) or E. coli K-12 DH1 (EFSA NDA Panel, 2023b).
Three more are currently being finalised – 3'-SL Kyowa, LNFP-I/2'FL, and 2'-FL Chr. Hansen – and there is also an application undergoing suitability checks on a beta-lactoglobulin produced by a GMM, he added.
