重组<i>链霉菌的</i>细胞毒性蒽环类代谢产物<i></i>,Journal of Natural Products

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重组链霉菌的细胞毒性蒽环类代谢产物
Journal of Natural Products ( IF 3.3 ) Pub Date : 2018-05-16 00:00:00 , DOI: 10.1021/acs.jnatprod.8b00212
Chun Gui _{1,

2} , Jie Yuan ₃ , Xuhua Mo ₄ , Hongbo Huang _{1,

2} , Shanwen Zhang _{1,

2} , Yu-Cheng Gu ₅ , Jianhua Ju _{1,

2}

Affiliation

最近从链霉菌属中分离了带有C7（C9或C10）-O - 1-罗丹明的蒽环类抗生素细胞溶菌素及其生物合成中间体。SCSIO1666。来自链霉菌基因组文库的粘粒p17C4被引入SCSIO 1666中，该库既包含l-若丹糖（或2- deoxy - 1 - fucose）的生物合成基因，又包含其糖基转移酶（由slgG编码）。应变链霉菌属。SCSIO 1666 / 17C4。该菌株次生代谢潜力的化学研究表明，生产了具有C7- O - 1的不同蒽环类抗生素-rhodinose（或2-脱氧升岩藻糖），而不是通常观察到1- rhodosamine。发酵液的纯化，产生12种新的蒽环类抗生素，包括三个新的ε紫红霉酮的衍生物，1，4，和8，九个新β紫红霉酮衍生物，2，3，5 - 7，和9 - 12，以及三个已知化合物，升-rhodinose-升-rhodinose-升-rhodinoserhodomycinone（13），ε紫红霉酮（14），和γ-紫红霉酮（15）。所有化合物均根据详细的光谱分析和与先前报道的数据进行比较而表征。这些化合物对一组人类癌细胞系表现出细胞毒性。值得注意的是，化合物4和13对HCT-116表现出明显的活性，其IC ₅₀值分别为0.3和0.2μM。这些IC ₅₀值与阳性对照表柔比星的IC ₅₀值相当。

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Cytotoxic Anthracycline Metabolites from a Recombinant Streptomyces

The C7 (C9 or C10)-O-l-rhodosamine-bearing anthracycline antibiotic cytorhodins and their biosynthetic intermediates were recently isolated from Streptomyces sp. SCSIO 1666. Cosmid p17C4 from the Streptomyces lydicus genomic library, which harbors both the biosynthetic genes for l-rhodinose (or 2-deoxy-l-fucose) and its glycosyltransferase (encoded by slgG), was introduced into SCSIO 1666 to yield the recombinant strain Streptomyces sp. SCSIO 1666/17C4. Chemical investigations of this strain’s secondary metabolic potential revealed the production of different anthracyclines featuring C7-O-l-rhodinose (or 2-deoxy-l-fucose) instead of the typically observed l-rhodosamine. Purification of the fermentation broth yielded 12 new anthracycline antibiotics including three new ε-rhodomycinone derivatives, 1, 4, and 8, nine new β-rhodomycinone derivatives, 2, 3, 5–7, and 9–12, and three known compounds, l-rhodinose-l-rhodinose-l-rhodinoserhodomycinone (13), ε-rhodomycinone (14), and γ-rhodomycinone (15). All compounds were characterized on the basis of detailed spectroscopic analyses and comparisons with previously reported data. These compounds exhibited cytotoxicity against a panel of human cancer cell lines. Significantly, compounds 4 and 13 displayed pronounced activity against HCT-116 as characterized by IC₅₀ values of 0.3 and 0.2 μM, respectively; these IC₅₀ values are comparable to that of the positive control epirubicin.

更新日期：2018-05-16

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