Lomaiviticins A and B, potent antitumor antibiotics from Micromonospora lomaivitiensis
Lomaiviticins A and B, potent antitumor antibiotics from Micromonospora lomaivitiensis
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DOI：
10.1021/ja010129o
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发表时间：
2001-06-06
影响因子：
15
通讯作者：
Carter, GT
中科院分区：
文献类型：
--
作者：
He, HY;Ding, WD;Carter, GT
早期对海洋海鞘Polysyncraton lithostrotum的研究导致分离出一种有效的抗肿瘤化合物，namenamicin。1由于其烯二炔苷元与放线菌衍生的卡奇霉素2和esperamicins 3中发现的烯二炔苷元非常相似，因此怀疑namenamicin的真实的生产者可能是微生物共生体。因此，从寄主海鞘的内核中分离到了一批放线菌，以回答复合起源的问题。4根据形态特征和16 S rDNA序列分析，鉴定出一株嗜盐放线菌LL-37 I366为小单孢菌属的一个新种，命名为“Micromonospora lomaiVitiensis”。5生物化学诱导试验（BIA）6表明，该微生物的发酵液显示出有效的DNA损伤活性，并且对一组癌细胞系具有极强的细胞毒性。7使用BIA引导的分级分离，分离出两种新的二聚重氮苯并芴糖苷，并将其命名为洛麦替星A（1）和B（2）（图1和3）。本文报道了新抗生素的生产、分离、结构鉴定和生物活性。在HP 20树脂存在下，通过菌株LL-37 I 366在海水培养基中发酵产生洛麦替星A（1）和B（2）。用酸性乙腈提取吸附在树脂上的粉红色混合物，并通过HPLC分离，得到纯抗生素1和2（实验和光谱数据，参见支持信息）。
An earlier study on the marine ascidian Polysyncraton lithostrotum resulted in the isolation of a potent antitumor compound, namenamicin. 1 Because of the remarkable similarity of its enediyne aglycon to that found in the actinomycete-derived calicheamicins2 and esperamicins, 3 it was suspected that the real producer of the namenamicin could be a microbial symbiont. Therefore, a number of actinomycetes were isolated from the inner core of the host ascidian to answer the question of compound origin. 4Among these actinomycetes, a halophilic strain, LL-37I366, was identified as a new species of the genus Micromonospora on the basis of its morphological properties and 16S rDNA sequence, and was named “Micromonospora lomaiVitiensis”. 5 The fermentation broth of this organism exhibited potent DNA-damaging activity indicated by the biochemical induction assay (BIA) 6 and was extremely cytotoxic against a panel of cancer cell lines. 7 Using BIA-guided fractionation, two novel dimeric diazobenzofluorene glycosides were isolated and designated lomaiviticins A (1) and B (2)(Figures 1 and 3). In this paper, the production, isolation, structural elucidation, and biological activity of the new antibiotics are reported. Lomaiviticins A (1) and B (2) were produced by fermentation of strain LL-37I366 in a seawater medium in the presence of HP20 resin. The pink colored mixture adsorbed on the resin was extracted with acidic acetonitrile and separated by HPLC to afford the pure antibiotics 1 and 2 (experimental and spectroscopic data, see Supporting Information).