从链霉菌属 Actinomadura 中分离、鉴定含恶唑啉的马杜拉菌素类铁载体及其生物活性分析

Isolation, characterization, and bioactivity profiling of oxazoline containing madurastatin siderophores from Actinomadura sp.

机构信息

Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Ohlebergsweg 12, 35392, Giessen, Germany.

Institute of Organic Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 17, 35392, Giessen, Germany.

出版信息

J Antibiot (Tokyo). 2022 Oct;75(10):576-582. doi: 10.1038/s41429-022-00557-z. Epub 2022 Sep 2.

DOI:10.1038/s41429-022-00557-z

PMID:36056265

Abstract

Nine new hydroxyphenyloxazolines, madurastatin B4, C2, D3 and D4, E1 and E2, F1 as well as G1 and G2 (8-16), along with two new enantiomers of madurastatin D1 (ent-6) and D2 (ent-7) and two known congeners, madurastatin B1 (2) and C1 (5), were isolated from the liquid culture of Actinomadura sp. ST100801 based on the initial activity against Escherichia coli screened in bicarbonate-supplemented Mueller Hinton II medium and identification via molecular networking. Structure elucidation was achieved by comprehensive 1D and 2D NMR as well as MS/MS fragmentation analyses. Their absolute configuration was determined by Marfey's analysis. Complemented with functionalized hydroxyphenyloxazolines (2, 4, 17-18) obtained by total synthesis, the isolated compounds were evaluated for antibacterial activities revealing MICs down to 4 µg ml against Moraxella catarrhalis. Therefore, this study enlarges the family of madurastatin siderophores.

摘要

从基于分子网络的在碳酸氢盐补充 Mueller Hinton II 培养基中筛选出的对大肠杆菌具有初始活性的放线菌 ST100801 的液体培养物中分离得到了 9 种新的羟基苯并恶唑啉类化合物 madurastatin B4、C2、D3 和 D4、E1 和 E2、F1 以及 G1 和 G2（8-16），以及 madurastatin D1（ent-6）和 D2（ent-7）的 2 种新对映异构体以及 2 种已知的同系物 madurastatin B1（2）和 C1（5）。结构阐明是通过全面的 1D 和 2D NMR 以及 MS/MS 碎片分析完成的。它们的绝对构型通过 Marfey 分析确定。通过全合成得到的功能化羟基苯并恶唑啉（2、4、17-18）进行补充，评估了分离得到的化合物的抗菌活性，结果表明对粘膜炎莫拉氏菌的 MIC 低至 4μg/ml。因此，本研究扩大了 madurastatin 类铁载体家族。