Aoki Y, Kondoh M, Nakamura M, Fujii T, Yamazaki T, Shimada H, Arisawa M
Nippon Roche Research Center, Kamakura, Japan.
J Antibiot (Tokyo). 1994 Aug;47(8):909-16. doi: 10.7164/antibiotics.47.909.
A new antifungal, azoxybacilin (an unusual amino acid with an azoxy moiety) was identified from Bacillus cereus, 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.
从蜡样芽孢杆菌中鉴定出一种新型抗真菌剂——偶氮氧芽孢杆菌素（一种带有偶氮氧部分的特殊氨基酸），并对其体外抗真菌活性及作用方式进行了研究。偶氮氧芽孢杆菌素对多种真菌具有活性。它对丝状真菌，如曲霉，尤为有效，且不显示抗菌活性。未观察到与目前市场上的抗真菌剂存在交叉耐药性。当向生长培养基中添加含硫氨基酸时，偶氮氧芽孢杆菌素对酿酒酵母的抗真菌活性的IC50值显著增大，而其他氨基酸则完全无效。因此，我们测试了这些氨基酸合成途径中涉及的中间体的作用。当培养基中存在以下四种中间体之一时：同型半胱氨酸、半胱氨酸、胱硫醚或甲硫氨酸，活性显著降低。这四种中间体与O - 乙酰高丝氨酸硫氢解酶突变体酿酒酵母ONO726生长所需的中间体相同，表明偶氮氧芽孢杆菌素会抑制硫固定途径中的一个或多个步骤。
