EM49 - NEW POLYPEPTIDE ANTIBIOTIC ACTIVE AGAINST CELL-MEMBRANES
EM49 - NEW POLYPEPTIDE ANTIBIOTIC ACTIVE AGAINST CELL-MEMBRANES
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DOI：
10.1111/j.1749-6632.1974.tb43286.x
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发表时间：
1974-01-01
影响因子：
5.2
通讯作者：
STROMING.JL
中科院分区：
文献类型：
--
作者：
MEYERS, E;PARKER, WL;STROMING.JL
抗生素的使用极大地帮助了微生物细胞结构和过程的阐明。例如，青霉素和其他抗生素是研究细菌细胞壁的合成和结构的重要帮助，放线菌素、双安霉素和利福霉素等抗生素被广泛用于核酸结构和代谢的研究。对于酵母和革兰氏阴性菌包膜的研究，多烯抗真菌抗生素制霉菌素和两性霉素 B 以及肽抗生素多粘菌素 B 具有重要价值。然而，显然需要用于此类调查的新工具。新抗生素的发现可以提供对重要细胞过程有新见解的方法。我们希望描述一种新抗生素 EM49，它对革兰氏阳性和革兰氏阴性细菌、酵母、真菌和原生动物具有广谱活性。我们已经证明，这种抗生素对大肠杆菌具有杀菌作用，并且它会对细胞包膜造成损害，这种损害可以通过电子显微镜检测到。因此，我们相信 EM49 将在细胞膜及其合成的研究中得到应用。这种抗生素由环状芽孢杆菌菌株产生，以脂八肽混合物的形式存在于发酵液中。抗生素在 6 N 盐酸中于 110" C 水解 16 小时后，释放出三种氨基酸。通过定量氨基酸分析和纸色谱法将其鉴定为 2, 4-二氨基丁酸、亮氨酸和苯丙氨酸。通过分离氨基酸并将其红外和核磁共振光谱与真实材料的比较来确认归属。氨基酸的摩尔比显示在表 1 中。光学589 和 224-225 nm 的旋转测量表明，苯丙氨酸具有 L-构型，而 2, 4-二氨基丁酸和亮氨酸以 D-和 L-构型存在。除了氨基酸之外，酸水解产物中还存在可醚提取的油。通过红外和核磁共振分析、质谱分析和气相色谱分析，该油由 C,,, 的混合物组成。当采用短水解时间（例如10-30分钟）时，羟基的乙酰化证明它在抗生素中是未取代的。C1，与C1，脂肪酸的比例为24：65。通过超速离心测定，游离碱的分子量约为1080。氨基酸的非整数量和脂肪酸级分的不均匀性表明抗生素。是紧密混合的
The elucidation of cellular structures and processes in microorganisms has been greatly assisted by the use of antibiotics.'For example, the penicillins and other antibiotics are important aids in the study of the synthesis and structure of bacterial cell walls, and antibiotics such as actinomycin, duanomycin, and rifamycin are being widely used in investigations of nucleic acid structure and metabolism. For the study of envelope membranes of yeasts and gram-negative bacteria, the polyene antifungal antibiotics, nystatin and amphotericin B, and the peptide antibiotic, polymyxin B, respectively, are of value. New tools for such investigations are, however, clearly desirable. The discovery of new antibiotics can provide the means for gaining new insights into vital cellular processes.We wish to describe a new antibiotic, EM49, that has a broad spectrum of activity against gram-positive and gram-negative bacteria, yeast, fungi, and protozoa. We have demonstrated that this antibiotic is bactericidal to Escherichia coli and that it causes damage to the cell envelope that is detectable by electron microscopy. We thus believe that EM49 will have applications in the study of cell membranes and their synthesis. This antibiotic, which is produced by a strain of Bacillus circulans, occurs in fermentation broths as a mixture of lipooctapeptides. Upon hydrolysis of the antibiotic in 6 N hydrochloric acid for 16 hr at 110" C, three amino acids are liberated. These were identified by quantitative amino acid analysis and paper chromatography as 2, 4-diaminobutyric acid, leucine, and phenylalanine. The assignments were confirmed by isolation of the amino acids and comparison of their infrared and nrnr spectra with those of authentic materials. The molar ratios of the amino acids are shown in TABLE 1. Optical rotation measurements at 589 and at 224-225 nm reveal that phenylalanine has the L-configuration, whereas 2, 4-diaminobutyric acid and leucine exist in both D-and L-configurations. In addition to the amino acids, an ether-extractable oil is also present in the acid hydrolysate. By infrared and nmr analyses, mass spectrometry, and gas chromatography, this oil was shown to consist of a mixture of C,,, and C,, 8-hydroxy fatty acids when short hydrolysis times (such as 10-30 min) had been employed. Acetylation of the hydroxyl group proved that it is unsubstituted in the antibiotic. The ratio of the C,, to C,, fatty acids is 24: 65. The molecular weight of the free base is approximately 1080, as determined by ultracentrifugation. The nonintegral quantities of the amino acids and the inhomogeneity of the fatty acid fraction suggested that the antibiotic is a mixture of closely