3 DEOXYGENATION IN THE BIOSYNTHESIS OF AROMATIC POLYKETIDES
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Deoxygenation reaction involved in the biosynthesis of fungal melanin was investigated by using synthesis, theoretical chemistry and enzymology. A biomimetic synthesis of scytalone (1), a simple derivative of tetralone, was reinvestigated and it was revealed that Scyatalone (1) is formed from 1,3,6,8-tetrahydroxynaphthalene (2; 1,3,6,8-THN) by sodium borohydride only in the presence of sodium methoxide. The reactive species of this reaction was clarified as a non-synmmetrical keto-tautomer, THN4H by NMR spectroscopy. The structure of the most stable ionic species of 1,3,6,8-THN (2) in CH_3ONa-CH_3OH was studied by the semi-empirical (AM1) and ab initio (Gaussian 86; 3-21+G//3-21G) molecular orbital calculations. It was suggested that the most stable species was a non-synmmetical keto-tautomeric trianion, which is in good agreement with the observations by NMR spectroscopy. Furthermore, transition state structures and stabilities were simulated for the hydride attack to the carbonyl carbons at C-1 and C-3 of THN4H. The results suggested that C-3 carbon was more favorable for the reduction, which coincided with the experimental fact. The enzymatic activities which reduce 1,3,6,8-THN and 1,3,8-trihydroxynaphthalene (1,3,8-THN) to scytalone (1) and vermelone (3) respectively, were detected in a cell free extract from shake cultures of Phialophora lagerbergii. The both reductive activities were observed in the same enzyme fractions in the partial purification using ammonium sulfate precipitation and DEAE cellulose column chromatography. Further purification and characterization of the enzyme are now in progress.
