Structure of aureobasidin A.

Abstract

Aureobasidin A, a new antifungal antibiotic, was isolated from the culture mediumof Aureobasidium pullulans R106. Aureobasidin A was a cyclic depsipeptide consisting of eight a-amino acid units and one hydroxy acid unit. The structures of the units were found by acid hydrolysis of the antibiotic to be 2 and L-phenyl-alanine. The sequence of the units was identified by NMRand FAB-MSof the products from the alkaline hydrolysis of aureobasidin A. 925Aureobasidins are complexes of antifungal antibiotics produced by Aureobasidium pullulans R106. The production, isolation, characterization, and antifungal activity of aureobasidins have been described in the preceding paper.1) In this paper, we report on the structure of aureobasidin A.Aureobasidin A (1, Fig. 1 The IR spectrum of 1 showed the presence of ester (1750cm"1) and amido carbonyls (1640cm"1). Mild alkaline hydrolysis (0.25 n NaOHin aqueous MeOH, room temperature, 25 hours) of 1 gave 2 and 3. Compounds 1 and 3 were negative in the ninhydrin color reaction and did not react with diazomethane or acetic anhydride in pyridine at room temperature. Compound 2 was also negative in the ninhydrin color reaction, but gave the methyl ester derivative 2a by treatment with diazomethane, and O-acetyl derivative 2b by treatment with acetic anhydride in pyridine. Further, 2a gave derivative 2c with O-acetyl and methyl ester groups when treated with acetic anhydride in pyridine.

Newly Discovered Neutral Glycosphingolipids in Aureobasidin A-resistant Zygomycetes

“…As shown in Fig. 1A, AbA strongly inhibits the growth of filamentous fungi such as A. oryzae, P. oxalicum, and Acremonium sp., previously reported for the yeast Saccharomyces cerevisiae (W303-1A) and other fungi (7)(8)(9)(10)13). However, growth inhibition by AbA was not observed for any Zygomycetes species such as M. hiemalis, R. microsporus, R. pusillus, and A. corymbifera (Fig.…”

“…We found that all Zygomycetes species tested were resistant to the antifungal agent Aureobasidin A, a cyclic depsipeptide produced by Aureobasidium pullulans (10). The Zygomycetes species do not have inositol-containing sphingolipids but contain novel neutral glycosphingolipids (GSLs) consisting glucose or galactose as sugar constituents.…”

Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P‐glycoproteins

“…During our search for peptide antibiotics which interact with human Pgp, we found that Saccharomyces cerevisiae expressing human MDRllPgp showed resistance to aureobasidin A, a new antifungal cyclic depsipeptide antibiotic produced by Aureobasidium pullulans R106 [15,16]. Surprisingly the overexpression of MDR2/Pgp also conferred resistance to aureobasidin A.…”

Existence of Unprocessed a Mitochondrial Enzyme: YDL178wp in the Membrane Fraction as an Oligomeric Formation with a Protein-Unfolding Activity

“…Cells were grown in YPD medium containing 0.5mg/ml of AbA [11] at 30 o C. Each samples treated with zymolyase 20T, then cells were homogenized and fractionated into mitochondrial [12] or post-mitochondrial fractions by using the centrifugation method as described in Methods section; the latter was usually used as the starting material for Unfold in preparation (Figure 1). In these experiments, mitochondrial and postmitochondrial samples were firstly examined using two column chromatography steps, Ni-NTA and ion exchange chromatography, followed by gel filtration chromatography, respectively.…”

“…The gene was fused at the C-terminal with hexahistidine-tag then amplified by PCR and then inserted into aureobasidine A (AbA) selective expression vector pAUR123 [11] (Takara BioChemicals). The protease-deficient yeast strain BY2778 [MATα prb1 -D1.6R pep4::HIS3 ura-3-52 his3-D200 can1 gal2] was transformed with this plasmid, grown in YPD medium containing 0.5 mg/ml of AbA at 30 o C. Cells were collected and treated with 2.5 mg/ml of zymolyase 20T then homogenized using glass pestle downs homogenizer.…”