Pseurotin A and 8-O-Demethylpseurotin A fromAspergillus fumigatusand Their Inhibitory Activities on Chitin Synthase

Bioscience, Biotechnology, and Biochemistry
1993.0

Abstract

Two inhibitors of chitin synthase were isolated from submerged cultures of an osmophilic Aspergillus fumigatus strain and identified as pseurotin A (1) and its 8-O-demethyl derivative (2). The two compounds inhibited both the solubilized and the membrane-bound forms of the enzyme, but do not have antifungal or antibacterial activities. The IC50 of pseurotin A was 81 μM for the solubilized enzyme. 8-O-Demethylpseurotin was less active with an IC50 of 192 μM. The structures of the compounds were elucidated by spectroscopical methods. During our search for selective antifungal compounds in cultures of higher fungi, a screening using solubilized chitin synthase (EC 2.4.1.16) from Coprinus cinereus was done. Enzyme-inhibiting activities were detected in the culture filtrate of an osmophilic Aspergillus fumigatus strain, HA 57-88. Two inhibitors were isolated from the culture filtrate of strain HA 57-88. One compound was identical to pseurotin A, the second proved to be a new derivative of pseurotin A, namely 8-O-demethylpseurotin A. In this paper, the taxonomy of the producing strain, the production, the isolation, the structural elucidation, and the enzyme-inhibiting activities of the two compounds (1, 2) are presented.

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