Pharmaceutical Research Center, Shionogi TechnoAdvance Research Co., Ltd., 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
Pharmaceutical Research Center, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
J Med Chem. 2020 Jun 11;63(11):6090-6095. doi: 10.1021/acs.jmedchem.0c00295. Epub 2020 May 19.
A novel lipopeptide antibiotic, stalobacin I (), was discovered from a culture broth of an unidentified Gram-negative bacterium. Stalobacin I () had a unique chemical architecture composed of an upper and a lower half peptide sequence, which were linked via a hemiaminal methylene moiety. The sequence of contained an unusual amino acid, carnosadine, 3,4-dihydroxyariginine, 3-hydroxyisoleucine, and 3-hydroxyaspartic acid, and a novel cyclopropyl fatty acid. The antibacterial activity of against a broad range of drug-resistant Gram-positive bacteria was much stronger than those of "last resort" antibiotics such as vancomycin, linezolid, and telavancin (MIC 0.004-0.016 μg/mL). Furthermore, compound induced a characteristic morphological change in Gram-positive and Gram-negative strains by inflating the bacterial cell body. The absolute configuration of a cyclopropyl amino acid, carnosadine, was determined by the synthetic study of its stereoisomers, which was an essential component for the strong activity of .
一种新型脂肽抗生素stalobacin I () 是从一种未鉴定的革兰氏阴性菌的培养液中发现的。stalobacin I () 具有独特的化学结构，由上半部分和下半部分肽序列组成，通过亚胺甲基部分连接。包含一个不寻常的氨基酸， carnosa 啶，3,4-二羟基精氨酸，3-羟基异亮氨酸和 3-羟基天冬氨酸，以及一种新型环丙基脂肪酸。化合物对广泛的耐药革兰氏阳性菌的抗菌活性比万古霉素、利奈唑胺和替拉万星等“最后手段”抗生素强得多（MIC 0.004-0.016 μg/mL）。此外，化合物通过使细菌细胞膨胀引起革兰氏阳性和革兰氏阴性菌株的特征形态变化。通过立体异构体的合成研究确定了环丙基氨基酸 carnosa 啶的绝对构型，这是化合物具有强活性的必要组成部分。
