Anthrol reductases: discovery, role in biosynthesis and applications in natural product syntheses.

Covering: up to 2023Short-chain dehydrogenase/reductases (SDR) are known to catalyze the regio- and stereoselective reduction of a variety of substrate types. Investigations of the deoxygenation of emodin to chrysophanol has led to the discovery of the anthrol reductase activity of an SDR, MdpC involved in monodictyphenone biosynthesis of Aspergillus nidulans and provided access to (R)-dihydroanthracenone, a putative biosynthetic intermediate. This facilitated the identification of several MdpC-related enzymes involved in the biosynthesis of aflatoxins B1, cladofulvin, neosartorin, agnestins and bisanthraquinones. Because of their ability to catalyze the reduction of hydroanthraquinone (anthrols) using NADPH, they were named anthrol reductases. This review provides a comprehensive summary of all the anthrol reductases that have been identified and characterized in the last decade along with their role in the biosynthesis of natural products. In addition, the applications of these enzymes towards the chemoenzymatic synthesis of flavoskyrins, modified bisanthraquinones, 3-deoxy anthraquinones, chiral cycloketones and ß-halohydrins have been discussed.

Synthesis of rhein and diacerein: a chemoenzymatic approach using anthrol reductase of Talaromyces islandicus.

Herein, we report two methods for the synthesis of the osteoarthritis drug rhein and its prodrug diacerein using a chemoenzymatic approach. The strategy relies on the use of an NADPH-dependent anthrol reductase of Talaromyces islandicus (ARti-2), which mediates the regioselective and reductive deoxygenation of anthraquinones. The work further implies similar biosynthesis of rhein in fungi.

Chemoenzymatic total synthesis of nodulones C and D using a naphthol reductase of Magnaporthe grisea.

Herein, the asymmetric and chemoenzymatic synthesis of (R)-nodulone C, cis-nodulone D and related (R)-dihydronaphthalenone is reported. It involves multistep chemical synthesis of putative biosynthetic substrates followed by regio- and stereoselective reduction using a NADPH-dependent tetrahydroxynaphthalene reductase of Magnaporthe grisea to obtain chiral nodulones in a biomimetic fashion.

Chemoenzymatic reduction of citreorosein and its implications on aloe-emodin and rugulosin C (bio)synthesis.

A chemoenzymatic reduction of citreorosein by the NADPH-dependent polyhydroxyanthracene reductase from Cochliobolus lunatus or MdpC from Aspergillus nidulans in the presence of Na2S2O4 gave access to putative biosynthetic intermediates, (R)-3,8,9,10-tetrahydroxy-6-(hydroxymethyl)-3,4-dihydroanthracene-1(2H)-one and its oxidized form, (R)-3,4-dihydrocitreorosein. Herein, we discuss the implications of these results towards the (bio)synthesis of aloe-emodin and (+)-rugulosin C in fungi.