Seven new and two known lipopeptides as well as five known polyketides: the activated production of silent metabolites in a marine-derived fungus by chemical mutagenesis strategy using diethyl sulphate.

Seven new and two known lipopeptides as well as five known polyketides: the activated production of silent metabolites in a marine-derived fungus by chemical mutagenesis strategy using diethyl sulphate.
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DOI:
10.3390/md12041815
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发表时间:
2014-03-28
期刊:
影响因子:
5.4
通讯作者:
Cui CB
Cui CB
中科院分区:
医学2区
文献类型:
--
作者:
Wu CJ;Li CW;Cui CB

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AD-2-1是由海洋来源的产紫青霉G59经硫酸二乙酯诱变获得的抗肿瘤真菌突变株。在使用K562细胞的MTT测定中,G59菌株最初不产生任何具有抗肿瘤活性的代谢物。通过与对照G59提取物直接比较,在MTT测定和TLC分析的指导下追踪新产生的代谢物,从突变体AD-2-1的提取物中分离出七种新的(1-7)和两种已知的(8-9)脂肽以及五种已知的聚酮化合物10-14。通过光谱和化学方法确定了7个新化合物的结构和绝对构型,命名为青霉木内酯A ~ G(1-7)。其中7个已知化合物被鉴定为fellucinase B(8)、fellucinase C(9)、1′-O-甲基laverantin(10)、averantin(11)、averufin(12)、nidurufin(13)和sterigmatocystin(14)。在MTT测定中,1-14在不同程度上抑制几种人癌细胞系。所有生物测定和HPLC-光电二极管阵列检测器(PDAD)-UV和HPLC-电子喷雾电离(ESI)-MS分析表明,突变体AD-2-1中1-14的产生是由原始G59真菌菌株中沉默代谢产物的活化产生引起的。目前的结果提供了额外的例子,使用硫酸二乙酯诱变的化学诱变策略的有效性,以发现新的化合物,通过激活沉默的代谢产物在真菌分离株。
AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1–7) and two known (8–9) lipopeptides were isolated together with five known polyketides 10–14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (1–7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1–14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1–14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.
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影响因子: 5.4
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发表时间: 1984-01-01
期刊: CARLSBERG RESEARCH COMMUNICATIONS
影响因子: --
作者:
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Purpurogemutantin 和 Purpurogemutantidin,新的补二甲环己烯酮衍生物,由通过硫酸二乙酯诱变海洋来源的青霉菌 G59 获得的突变体产生
DOI: 10.3390/md10061266
发表时间: 2012-06-01
期刊: MARINE DRUGS
影响因子: 5.4
作者:
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