Biosynthesis of nanaomycin. III. Nanaomycin A formation from nanaomycin D by nanaomycin D reductase via a hydroquinone.
Nanaomycin D reductase which is involved in the biosynthesis of the antifungal antibiotic nanaomycin catalyzes the formation of nanaomycin A from nanaomycin D in the presence of NADH under anaerobic conditions. On the other hand, under aerobic conditions NADH is consumed and nanaomycin A formation is markedly reduced. These findings suggest that nanaomycin A synthesis is not due to the direct reduction of the 5-membered lactone ring of nanaomycin D. Reduction of various quinones by the enzyme was examined. It was found that nanaomycin A is converted to its hydroquinone derivative in the presence of NADH under anaerobic conditions, whereas NADH consumption alone is observed under aerobic conditions. When p-benzoquinone, 1,4-naphthoquinone or menadione is used instead of nanaomycin D, NADH is also consumed. These results indicate that: (1) these compounds act as electron acceptors, (2) O2 functions as final electron acceptor under aerobic conditions, and (3) nanaomycin D reductase is, in fact, an NADH dehydrogenase (quinone). Changes in the UV-absorption spectrum of a reaction mixture containing nanaomycin D and NADH indicate that a hydroquinone derivative is formed as an intermediate during nanaomycin A formation. Similar results were obtained when nanaomycin D is reduced chemically with NaBH4 or Zn powder. It was concluded that nanaomycin D is converted to a hydroquinone derivative and that nanaomycin A is then formed nonenzymatically through intramolecular electron transfer.
D000332:Aerobiosis; D000693:Anaerobiosis; D000935:Antifungal Agents / Q000096:biosynthesis*; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D006873:Hydroquinones / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D009285:Naphthoquinones / Q000096:biosynthesis / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D000095622:Benzoisochromanequinones
D000935:Antifungal Agents; D006873:Hydroquinones; D009245:NADH Dehydrogenase; D009285:Naphthoquinones; D010088:Oxidoreductases; C008638:nanaomycin A; D000095622:Benzoisochromanequinones; C013079:kalafungin; C032455:nanaomycin D reductase