How is vitamin C produced?

Chemical synthesis today constitutes the primary production method for vitamin C, for both pharmaceutical and cosmetic applications. It is primarily based on the Reichstein process, developed in the 1930s and still employed, in optimised forms, on an industrial scale. This process enables the conversion of D-glucose, most commonly derived from maize starch, into L-ascorbic acid, the biologically active form of vitamin C.

Synthetic vitamin C is strictly identical, both chemically and biologically, to the vitamin C naturally present in plants.

Several consecutive steps are required, combining organic chemistry and biotechnology, in order to obtain the correct stereoisomer. Initially, glucose is hydrogenated into D-sorbitol using a Raney nickel catalyst. This sorbitol is then oxidised by microbial fermentation to yield L-sorbose, a key step that ensures the correct stereochemical configuration of the molecule. The hydroxyl groups of L-sorbose are then protected by forming acetals in the presence of acetone and sulphuric acid at low temperature, before a chemical oxidation classically carried out with potassium permanganate under alkaline conditions.

The final step involves the closure of the lactone ring, allowing the formation of ascorbic acid. It can be achieved either by heating in an aqueous medium or by esterification followed by treatment with sodium methoxide, before a final acidification. More modern variants of the process also include a direct oxidation in the presence of oxygen and a platinum catalyst, aimed at improving yields.

At Typology, we use stable derivatives of vitamin C obtained from D-glucose via the Reichstein–Grüssner process, combining chemical steps and a microbiological step.

Bacterial fermentation represents an attractive alternative to chemical synthesis for the industrial production of vitamin C. It does not, in most cases, yield ascorbic acid directly but aims to produce its immediate precursor, 2-keto-L-gulonic acid (2-KGA), which is subsequently chemically converted into vitamin C. For this purpose, complementary micro-organisms must be used, such as Gluconobacter oxydans, Ketogulonicigenium vulgare and various species of Bacillus.

Indeed, K. vulgare is capable of producing 2-KGA, but this bacterium can only function optimally in the presence of auxiliary strains, such as Bacillus. The latter provide essential metabolites, siderophores that facilitate iron uptake, and help to mitigate the oxidative stress to which K. vulgare is highly sensitive. Proteomic and metabolomic analyses have shown that sporulation, i.e. the release of spores, and the partial lysis of Bacillus release nutrients essential for the growth and metabolic activity of K. vulgare, thus improving the yields of 2-KGA production.

This process is recognised for its efficacy but presents significant industrial constraints, such as prolonged fermentation times and additional sterilisation phases.

Recently, advances in metabolic engineering have simplified this scheme by developing fermentations based on better-controlled synthetic microbial consortia. For example, the genetic modification of G. oxydans to limit its consumption of sorbitol reduces competition with K. vulgare and strengthen their mutualism. Other studies have also shown that it is possible to produce vitamin C directly from glucose using genetically modified bacteria, such as Escherichia coli expressing plant biosynthetic genes, although these yields remain insufficient for industrial application.

Finally, vitamin C can be obtained by extraction from natural sources, such as fruits, vegetables, certain leaves or even algae. Historically, this route relied mainly on conventional aqueous or acid-based extractions, which were effective but sometimes lengthy, energy-intensive and poorly selective. In recent years, the development of so-called “green” extraction techniques has renewed interest in this approach, seeking to reconcile yield, respect for the environment and the preservation of this molecule particularly sensitive to oxidation and heat.

Among these innovative techniques are ultrasound-assisted extraction, microwave-assisted extraction, pressurised-liquid extraction and supercritical-fluid extraction. They rely on the use of gentle conditions and eco-compatible solvents, such as water or mildly acidified solutions. Several studies demonstrate the efficacy of these approaches. For instance, vitamin C extraction from camu-camu, a fruit naturally rich in ascorbic acid, has shown that acid extraction can achieve high yields, while pressurised-liquid extraction provides a cleaner and more controlled alternative. Likewise, optimisation of microwave-assisted extraction, particularly using citric-acid-based solutions, has yielded high extraction rates from vegetables such as bok choy, whilst limiting vitamin C oxidation.

If natural extraction is more complex to standardise on a large scale than chemical synthesis, it nonetheless represents a relevant avenue that will need to be explored in the future for food, pharmaceutical and cosmetic applications.

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