Production of Hydroxy Acids: Selective Double Oxidation of Diols by Flavoprotein Alcohol Oxidase

Abstract

Flavoprotein oxidases can catalyze oxidations of alcohols and amines by merely using molecular oxygen as the oxidant, making this class of enzymes appealing for biocatalysis. The FAD‐containing (FAD=flavin adenine dinucleotide) alcohol oxidase from P. chrysosporium facilitated double and triple oxidations for a range of aliphatic diols. Interestingly, depending on the diol substrate, these reactions result in formation of either lactones or hydroxy acids. For example, diethylene glycol could be selectively and fully converted into 2‐(2‐hydroxyethoxy)acetic acid. Such a facile cofactor‐independent biocatalytic route towards hydroxy acids opens up new avenues for the preparation of polyester building blocks.

Natural Flavins: Occurrence, Role, and Noncanonical Chemistry

“…G: Condensation of (6) and L-3,4-dihydroxybutan-2-one 4-phosphate (10) by 6,7-dimethyl-8-ribityllumazine synthase, forms 6,7-dimethyl-8-(D-ribityl)lumazine (7). H: two equivalents of (7) are condensed to form one equivalent of riboflavin (8) and one equivalent of (6). I: 3,4-dihydroxy 2-butanone 4-phosphate synthase catalyzes the formation of (10) out of R5P (9).…”

“…Since their discovery about a century ago [1], these flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) utilizing oxidoreductases have been well studied, and currently much is known about flavin chemistry. Some examples of the wide range of reactions catalyzed by flavins include: reduction of activated C=C double bonds [2], oxidation of alcohols [3,4], oxidations and reductions of aldehydes [5,6] and lactols [7,8], as well as (cyclic) alkane hydroxylation [9], aromatic hydroxylation [10,11], Baeyer-Villiger oxidation [12,13], epoxidation, sulfoxidation, phosphite ester, selenide, organoboron, and amine oxidations [14], dehalogenation, halogenation [15], decarboxylation [16,17], and even light production [18]. Part of the chemical versatility is derived from the ability to undergo both one-and two-electron reduction/oxidation reactions, to form several thermodynamically and kinetically accessible stable redox states [19].…”

“…Figure 2.2 Riboflavin biosynthesis pathway. Riboflavin(8) is synthesized out of one equivalent of GTP(1) and two equivalents of ribulose-5-phosphate (R5P (9)). A: The C8 and two phosphate groups of GTP are hydrolyzed by GTP cyclohydrolase II, forming pyrophosphate, formate, and 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)one(2).…”