Diversity in Reduction with Short‐Chain Dehydrogenases: Tetrahydroxynaphthalene Reductase, Trihydroxynaphthalene Reductase, and Glucose Dehydrogenase

Abstract

NAD(P)H‐dependent oxidoreductases from the short‐chain dehydrogenases/reductases (SDRs) family possess high functional diversity. Three SDRs, namely, tetrahydroxy‐ and trihydroxynaphthalene reductases (T4HNR, T3HNR) involved in the dihydroxynaphthalene‐melanin biosynthesis of the phytopathogenic fungus Magnaporthe grisea, and glucose dehydrogenase (GDH) from Bacillus subtilis, were characterized regarding their substrate range and functional behavior. T4HNR and T3HNR share activities towards the stereoselective reduction of 2‐tetralone derivatives and 2,3‐dihydro‐1,4‐naphthoquinones and show distinct but different stereochemical outcome in the case of epoxy‐1,4‐napthoquinones as substrates. GDH shares the activity towards 2,3‐dihydro‐1,4‐naphthoquinones, however, with low stereocontrol. Moreover, GDH reduces 2‐hydroxy‐2,3‐dihydro‐1,4‐naphthoquinone into trans‐4‐hydroxyscytalone with a high diastereomeric excess (96 %), whereas T4HNR gave the cis diastereomer (diastereomeric excess>99 %). Thus, SDRs provide a much higher functional and stereochemical diversity than previously thought, already exemplified by many transformations of three members of this enzyme family.

Extended Catalytic Scope of a Well‐Known Enzyme: Asymmetric Reduction of Iminium Substrates by Glucose Dehydrogenase

“…The high reactivity of the iminium salts towards reduction was probably helpful for elucidation of the entirely unexpected asymmetric reduction of a C=N bond by GDH, usually regarded as a “classical” NADPH‐dependent SDR . Hence, we have demonstrated that the substrate scope of GDH is broader than initially suspected, underscoring our previous finding of GDH‐catalyzed reduction of naphthoquinone derivatives . The enantioselectivity of the iminium reduction is strikingly high, even being higher than for many IRED‐catalyzed transformations.…”

“…Glucose dehydrogenase (GDH), a prototypical member of the SDR family, for example, was previously thought solely to catalyze NAD(P)‐dependent oxidation of d ‐glucose to gluconolactone . Until recently, GDH was not known to be active with non‐sugar substrates …”

Biocatalytic Properties and Structural Analysis of Phloroglucinol Reductases

“…Thed earomatization reaction is enabled by the 1,3,5-arrangement of the three hydroxy groups of 1,w hich results in at endency towards distinct tautomerization and thus favors nucleophilic attack on the oxo carbon groups. [8] Patel et al have shown the NADPH-dependent reduction of 1 into 2 by ap artially purified phloroglucinol reductase (PGR) from Coprococcus sp., which has am olecular weight of about 130 kDa. [7] Such biocatalytic dearomatization reactions are frequently found in the bio-synthesis of secondary metabolites as at ool for deoxygenation, which in this case would result in resorcinol (3; Scheme 2).…”

“…[9] Fermentative degradation of gallic acid (4), pyrogallol (5), 2,4,6-trihydroxybenzoic acid (6), and 1 was reported in apure culture of Pelobacter acidigallici gen. nov.s p. nov. [10,11] Here too,the pathway was assumed to proceed via 2. [8,[15][16][17][18] Theenzymatic dearomatization of polyhydroxylated benzenes should be possible in as imilar manner. [3,12,13] Haddock and Ferry have described the purification of aPGR from the cell extract of E. oxidoreducens.The described enzyme,which has an ative molecular weight of 78 kDa (homodimer), was specific for 1 and NADPH.…”

Bonding (especially C−C bonding) with Woody Fessner

“…The group of Vladimir Kren has been active in oligosaccharide synthesis for years and provides a contribution on prokaryotic and eukaryotic aryl sulfotransferases and their use in sulfation of quercetin . The group of Michael Müller in Freiburg point out that short chain dehydrogenases have a much higher functional and stereochemical diversity than had been previously thought …”