Chemo-enzymatic synthesis of sugar acid by pyranose 2-oxidase

Abstract

Aldonic acids are valuable raw materials in the pharmaceutical, food, cosmetic, and construction industries. Herein, we report the biocatalytic synthesis of aldonic acids using pyranose 2-oxidase (P2O) to catalyze the key oxidation step of the sugar precursors. The reactions of P2O with monosaccharides in the presence of oxygen as an electron acceptor can result in the 2-keto, 2-keto sugar lactone, and 2-keto sugar acids, which can be further reduced to yield the corresponding aldonic acids. These chemo-enzymatic reactions can convert D-galactose and L-arabinose to galactonic acid and arabinoic acid, respectively, with a >99% conversion. We used methylation and high-resolution mass spectrometry to identify the product structures. Results of molecular docking and structural analysis explain how P2O controls the mechanism and regio-selectivity of the second oxidation of keto-sugars. The monosaccharides with OH at the C4 equatorial position favor C3 second oxidation, while the monosaccharides with C4-OH at the axial position favor C1 second oxidation. The data presented here explain for the first time at the molecular level how a sugar oxidase such as P2O produces two double oxidation products when different sugars are used as substrates.