Abstract：
Four compounds (1-4) featuring with an L-rhodinose and spiroketal, possess uncommon continuous hydroxy groups in the macrolide skeleton, and a dichloro-diketopiperazine (5) were isolated from a marine derived Micromonospora sp. FIMYZ51. The determination of the relative and absolute configurations of all isolates was achieved by extensive spectroscopic analyses, single-crystal X-ray diffraction analysis, and ECD calculations. According to structural characteristic and genomic sequences, a plausible biosynthetic pathway for compound 1-4 was proposed and a spirocyclase was inferred to be responsible for the formation of the rare spirocyclic moiety. Compounds 1-4 exhibited potent antifungal activities which is equal to itraconazole against Aspergillus niger. Compounds 1-5 exhibited different degree of inhibitory activities against opportunistic pathogenic bacteria of endocarditis (Micrococcus luteus) with MIC values ranging from 0.0625 μg/mL to 32 μg/mL. Compounds 2 and 3 showed moderate cytotoxicity against drug-resistant tumor cell lines (Namalwa and U266). The result not only provides active lead-compounds, but also reveal the potential of the spirocyclase gene resources from Micromonospora sp., which highlights the promising potential of the strain for biomedical applications.
摘要：
四个化合物（1-4）的特点与L-罗地糖和螺缩酮，在大环内酯骨架中具有罕见的连续羟基，和二氯二酮哌嗪（5）从海洋衍生的小单孢菌中分离。FIMYZ51.所有分离物的相对和绝对构型的确定是通过广泛的光谱分析来实现的，单晶X射线衍射分析,和ECD计算。根据结构特征和基因组序列，提出了化合物1-4的合理生物合成途径，并推断螺环酶负责罕见螺环部分的形成。化合物1-4对黑曲霉的抗真菌活性与伊曲康唑相同。化合物1~5对条件致病菌(黄体微球菌)具有不同程度的抑制活性,MIC值为0.0625μg/mL~32μg/mL。化合物2和3对耐药肿瘤细胞系(Namalwa和U266)显示出中等的细胞毒性。结果不仅提供了活性的先导化合物，而且还揭示了来自小单孢菌的螺环化酶基因资源的潜力。,这凸显了该菌株在生物医学应用中的潜力。
