Transferring Fungi to a Deuterium-Enriched Medium Results in Assorted, Conditional Changes in Secondary Metabolite Production.
Transferring Fungi to a Deuterium-Enriched Medium Results in Assorted, Conditional Changes in Secondary Metabolite Production.
复制标题
DOI：
10.1021/acs.jnatprod.5b00337
复制
发表时间：
2015-06-26
影响因子：
5.1
通讯作者：
Cichewicz RH
中科院分区：
文献类型：
--
作者：
Wang B;Park EM;King JB;Mattes AO;Nimmo SL;Clendinen C;Edison AS;Anklin C;Cichewicz RH
氘是少数几种能够显著改变化合物化学和生物特性的稳定同位素之一。一个中子加到一个<$原子上会导致其质量几乎加倍，这就产生了氘的特征同位素效应。由于将氘掺入有机底物中已知会改变酶/蛋白质-底物相互作用，因此我们测试了氘富集会在多大程度上改变真菌次级代谢产物的产生。测试了几种真菌培养物，在所有情况下，它们的次级代谢物组都以天然产物生产的变化为标志。在氘富集条件下生长的一种曲霉菌的后处理导致产生了以前从未从真菌中检测到的几种次级代谢产物。生物测定测试显示，与在非氘富集条件下生长真菌得到的无活性粗真菌提取物相比，在氘富集培养基中培养的相同分离株得到的提取物抑制耐甲氧西林金黄色葡萄球菌。使用各种NMR和质谱实验，我们能够将细菌抑制剂鉴定为色素A的同位素标记版本（6）。从该真菌中还获得了另外五种同位素标记的代谢产物，包括短梗霉酰胺F（1）、千金藤菌素A（2）、notoamide D（3）、notoamide L（4）和notoamide C（5）。考虑到在氘富集环境中生长的这种真菌和其他真菌的次级代谢产物谱中观察到的各种变化，以及以前从未从本研究中使用的曲霉属分离株中观察到1和3-6的事实，我们提出氘富集可能提供进一步扩大真菌化学多样性潜力的有效方法。
Deuterium is one of the few stable isotopes that have the capacity to significantly alter a compound’s chemical and biological properties. The addition of a single neutron to a protium atom results in the near doubling of its mass, which gives rise to deuterium’s characteristic isotope effects. Since the incorporation of deuterium into organic substrates is known to alter enzyme/protein–substrate interactions, we tested the extent to which deuterium enrichment would modify fungal secondary metabolite production. Several fungal cultures were tested, and in all cases their secondary metabolomes were marked by changes in natural product production. Workup of one Aspergillus sp. grown under deuterium-enrichment conditions resulted in the production of several secondary metabolites not previously detected from the fungus. Bioassay testing revealed that in comparison to the inactive crude fungal extract derived from growing the fungus under non-deuterium-enriched conditions, an extract derived from the same isolate cultured in a deuterium-enriched medium inhibited methicillin-resistant Staphylococcus aureus. Using an assortment of NMR and mass spectrometry experiments, we were able to identify the bacterial inhibitor as an isotope-labeled version of pigmentosin A (6). Five additional isotopically labeled metabolites were also obtained from the fungus including brevianamide F (1), stephacidin A (2), notoamide D (3), notoamide L (4), and notoamide C (5). Given the assorted changes observed in the secondary metabolite profiles of this and other fungi grown in deuterium-enriched environments, as well as the fact that 1 and 3–6 had not been previously observed from the Aspergillus sp. isolate used in this study, we propose that deuterium enrichment might offer an effective method for further expanding a fungus’s chemical diversity potential.
登录
查看更多内容
影响因子：
5.1
作者：
Wang, Bin;You, Jianlan;King, Jarrod B.;Cai, Shengxin;Park, Elizabeth;Powell, Douglas R.;Cichewicz, Robert H.
通讯作者：
Cichewicz, Robert H.
影响因子：
1.1
作者：
Elix, JA;Wardlaw, JH
通讯作者：
Wardlaw, JH
影响因子：
4
作者：
Paliy, O;Bloor, D;Barber, J
通讯作者：
Barber, J
Notoamides A-D:: 从一种源自海洋的真菌 Aspergillus sp.
影响因子：
16.6
作者：
Kato, Hikaru;Yoshida, Takushi;Tsukamoto, Sachiko
通讯作者：
Tsukamoto, Sachiko
影响因子：
5.2
作者：
Tsukamoto S;Kawabata T;Kato H;Greshock TJ;Hirota H;Ohta T;Williams RM
通讯作者：
Williams RM