Activation of the dormant secondary metabolite production by introducing gentamicin-resistance in a marine-derived Penicillium purpurogenum G59.
Activation of the dormant secondary metabolite production by introducing gentamicin-resistance in a marine-derived Penicillium purpurogenum G59.
复制标题
通过在海洋来源的紫青霉 G59 中引入庆大霉素抗性来激活休眠的次生代谢产物生产
DOI：
10.3390/md10030559
复制
发表时间：
2012-03
期刊：
影响因子：
5.4
通讯作者：
Hua W
中科院分区：
文献类型：
--
作者：
Chai YJ;Cui CB;Li CW;Wu CJ;Tian CK;Hua W
一种新的方法来激活沉默的基因簇休眠的次级代谢产物的生产已被开发，通过引入庆大霉素抗性，原来是无效的，海洋来源的真菌菌株产紫青霉G59。在用高浓度庆大霉素的DMSO水溶液处理G59孢子后，通过单菌落分离获得总共181个突变体。与菌株G59相比，9个突变体培养物的EtOAc提取物对K562细胞显示出抑制作用，表明9个突变体已经获得产生抗肿瘤代谢产物的能力。这通过G59和9种突变体的EtOAc提取物的TLC和HPLC分析得到证实。进一步的分离和鉴定表明，突变株5-1-4产生了4种新的抗肿瘤次生代谢产物：janthinone（1）、fructigenine A（2）、asperric acid methyl ester（3）和citrinin（4），这4种化合物在其他产紫青霉（Penicillium purpurogenum）的次生代谢产物中也没有发现。而化合物1-4对K562细胞的增殖有抑制作用，在100 μg/mL时抑制率分别为34.6%（1）、60.8%（2）、31.7%（3）和67.1%（4）。本研究证明了一种简单而实用的通过引入对氨基糖苷类抗生素的获得性耐药性来激活休眠真菌次级代谢产物产生的方法的有效性，该方法可应用于诱导真菌休眠代谢潜力以获得隐藏次级代谢产物的研究。
A new approach to activate silent gene clusters for dormant secondary metabolite production has been developed by introducing gentamicin-resistance to an originally inactive, marine-derived fungal strain Penicillium purpurogenum G59. Upon treatment of the G59 spores with a high concentration of gentamicin in aqueous DMSO, a total of 181 mutants were obtained by single colony isolation. In contrast to the strain G59, the EtOAc extracts of nine mutant cultures showed inhibitory effects on K562 cells, indicating that the nine mutants had acquired capability to produce antitumor metabolites. This was evidenced by TLC and HPLC analysis of EtOAc extracts of G59 and the nine mutants. Further isolation and characterization demonstrated that four antitumor secondary metabolites, janthinone (1), fructigenine A (2), aspterric acid methyl ester (3) and citrinin (4), were newly produced by mutant 5-1-4 compared to the parent strain G59, and which were also not found in the secondary metabolites of other Penicillium purpurogenum strains. However, Compounds 1–4 inhibited the proliferation of K562 cells with inhibition rates of 34.6% (1), 60.8% (2), 31.7% (3) and 67.1% (4) at 100 μg/mL, respectively. The present study demonstrated the effectiveness of a simple, yet practical approach to activate the production of dormant fungal secondary metabolites by introducing acquired resistance to aminoglycoside antibiotics, which could be applied to the studies for eliciting dormant metabolic potential of fungi to obtain cryptic secondary metabolites.
登录
查看更多内容
海洋源性内生真菌 Penicillium chrysogenum QEN-24S 的次生代谢物
影响因子：
5.4
作者：
Gao SS;Li XM;Du FY;Li CS;Proksch P;Wang BG
通讯作者：
Wang BG
影响因子：
14.8
作者：
Bergmann, Sebastian;Schuemann, Julia;Hertweck, Christian
通讯作者：
Hertweck, Christian
影响因子：
3.3
作者：
Chen, GH;Wang, GYS;Davies, J
通讯作者：
Davies, J
DOI：
10.1016/0005-2736(92)90139-d
发表时间：
1992-02-17
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ANCHORDOGUY, TJ;CARPENTER, JF;CROWE, LM
通讯作者：
CROWE, LM
影响因子：
64.8
作者：
Bentley, SD;Chater, KF;Hopwood, DA
通讯作者：
Hopwood, DA