Synthesis of the antibiotic cortalcerone from D-glucose using pyranose 2-oxidase and a novel fungal enzyme, aldos-2-ulose dehydratase.
Using two enzymes purified from the white-rot fungus, Polyporus obtusus, 5% solutions of D-glucose have been quantitatively converted in vitro into D-arabino-hexos-2-ulose (D-glucosone) and subsequently into a compound having antimicrobial activity. The antibiotic has been shown by nuclear magnetic resonance and mass spectroscopy to be chemically identical to a previously described fungal metabolite known as cortalcerone. Based on kinetic analysis of the synthetic process, a pathway for the biosynthesis of cortalcerone is proposed, involving both chemical rearrangement and enzymically catalyzed steps. Two enzymes, pyranose 2-oxidase and a previously uncharacterized D-arabino-hexos-2-ulose-utilizing enzyme, may be sufficient for the biosynthesis of cortalcerone from glucose in vivo. The D-arabino-hexos-2-ulose-utilizing enzyme dehydrates certain aldosuloses and has been named aldos-2-ulose dehydratase. The enzyme, which appears to be a dimer of 95-kDa subunits, has been purified 450-fold. Additional properties of aldos-2-ulose dehydratase are described, including its apparent ability to catalyze two different steps in the proposed biosynthetic pathway for cortalcerone.
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Cetus Corporation, Department of Protein Chemistry, Emeryville, California 94608.
Halenbeck
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Moreland
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D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002237:Carbohydrate Dehydrogenases / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D011124:Polyporaceae / Q000737:chemistry / Q000201:enzymology*; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry; D011753:Pyrones
D000900:Anti-Bacterial Agents; D011714:Pyrans; D011753:Pyrones; C077712:cortalcerone; D002237:Carbohydrate Dehydrogenases; C022489:pyranose oxidase; D005947:Glucose