Industrial Production of l-Ascorbic Acid (Vitamin C) and d-Isoascorbic Acid

l-ascorbic acid (vitamin C) was first isolated in 1928 and subsequently identified as the long-sought antiscorbutic factor. Industrially produced l-ascorbic acid is widely used in the feed, food, and pharmaceutical sector as nutritional supplement and preservative, making use of its antioxidative properties. Until recently, the Reichstein–Grüssner process, designed in 1933, was the main industrial route. Here, d-sorbitol is converted to l-ascorbic acid via 2-keto-l-gulonic acid (2KGA) as key intermediate, using a bio-oxidation with Gluconobacter oxydans and several chemical steps. Today, industrial production processes use additional bio-oxidation steps with Ketogulonicigenium vulgare as biocatalyst to convert d-sorbitol to the intermediate 2KGA without chemical steps. The enzymes involved are characterized by a broad substrate range, but remarkable regiospecificity. This puzzling specificity pattern can be understood from the preferences of these enyzmes for certain of the many isomeric structures which the carbohydrate substrates adopt in aqueous solution. Recently, novel enzymes were identified that generate l-ascorbic acid directly via oxidation of l-sorbosone, an intermediate of the bio-oxidation of d-sorbitol to 2KGA. This opens the possibility for a direct route from d-sorbitol to l-ascorbic acid, obviating the need for chemical rearrangement of 2KGA. Similar concepts for industrial processes apply for the production of d-isoascorbic acid, the C5 epimer of l-ascorbic acid. d-isoascorbic acid has the same conformation at C5 as d-glucose and can be derived more directly than l-ascorbic acid from this common carbohydrate feed stock.