A NEW METHIONINE ANTAGONIST THAT HAS ANTIFUNGAL ACTIVITY: MODE OF ACTION

A new antifungal, azoxybacilin (an unusual amino acid with an azoxy moiety) was identified from Bacillus cereusd, and its in vitro antifungal activity and mode of action were investigated. Azoxybacilin was active against a broad spectrum of fungi. It was especially active against mycelial fungi, such as Aspergillus, and did not show antibacterial activity. No cross-resistance with antifungals currently on the market was observed. The IC50 values of azoxybacilin antifungal activity against Saccharomyces cerevisiae were significantly greater when amino acids containing sulfur were added to the growth medium, whereas other amino acids were not effective at all. We, therefore, tested the effect of the intermediates involved in the synthetic pathway of these amino acids. The activity markedly diminished when one of the following four intermediates was present in the medium: homocysteine, cysteine, cystathionine or methionine. These four intermediates were the same as those required for the growth of the O-acetylhomoserine sulfhydrylase mutant, S. cerevisiae ONO726, indicating that azoxybacilin would inhibit a step or steps in the sulfur-fixation pathway.