title: Unprecedented role of hydronaphthoquinone tautomers in biosynthesis.
abstract: Quinones and hydroquinones are among the most common cellular cofactors, redox mediators, and natural products. Here, we report on the reduction of 2-hydroxynaphthoquinones to the stable 1,4-diketo tautomeric form of hydronaphthoquinones and their further reduction by fungal tetrahydroxynaphthalene reductase. The very high diastereomeric and enantiomeric excess, together with the high yield of cis-3,4-dihydroxy-1-tetralone, exclude an intermediary hydronaphthoquinone. Labeling experiments with NADPH and NADPD corroborated the formation of an unexpected 1,4-diketo tautomeric form of 2-hydroxyhydronaphthoquinone as a stable intermediate. Similar 1,4-diketo tautomers of hydronaphthoquinones were established as products of the NADPH-dependent enzymatic reduction of other 1,4-naphthoquinones, and as substrates for different members of the superfamily of short-chain dehydrogenases. We propose an essential role of hydroquinone diketo tautomers in biosynthesis and detoxification processes.
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany); Present address: Centre of Biomedical Research, Raebareli Road, Lucknow 226 014, Uttar Pradesh (India).
authors.forename: Syed Masood
authors.initials: SM
authors.lastname: Husain
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schätzle
authors.forename: Steffen
authors.initials: S
authors.lastname: Lüdeke
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
mesh_terms: D002384:Catalysis; D006873:Hydroquinones; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism*; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D006873:Hydroquinones; D009285:Naphthoquinones; D011809:Quinones; C031927:hydroquinone
keywords: dearomatization; diversity-oriented synthesis; enzyme catalysis; hydroquinones; reaction mechanisms