Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds.
Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds.
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DOI：
10.1021/acs.jnatprod.5b01014
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发表时间：
2016-02-26
影响因子：
5.1
通讯作者：
Cech, Nadja B.
中科院分区：
文献类型：
--
作者：
Kellogg, Joshua J.;Todd, Daniel A.;Egan, Joseph M.;Raja, Huzefa A.;Oberlies, Nicholas H.;Kvalheim, Olav M.;Cech, Nadja B.
天然产物研究的一个核心挑战是从复杂的混合物中分配生物活性化合物。解决这一挑战的黄金标准方法，生物测定引导的分级分离，往往偏向于丰富的，而不是生物活性的混合物成分。本研究评价了生物测定指导的分馏与非靶向代谢物谱分析的组合，以改善分馏过程早期的活性组分鉴别。这种方法的关键是综合生物和化学数据集的统计建模（生物化学计量分析）。比较了偏最小二乘加载向量法、S图法和选择性比法三种生物化学计量学数据分析方法。内生真菌链格孢属和核壳菌属的提取物对金黄色葡萄球菌具有抗微生物活性。结合选择性比率的生物化学计量学分析在分级过程的早期从这些提取物中鉴定生物活性离子方面表现最好，产生作为来自链格孢属物种和核壳属物种的抗菌成分的交替色丁（3，MIC 0.23 μg/mL）和大球内酯A（4，MIC 75 μg/mL），分别这项研究表明，生物化学计量学结合生物测定指导分馏，以确定生物活性混合物成分的潜力。这种方法的一个好处是能够将分级分离和生物测定数据的多个阶段整合到单个分析中。
A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased towards abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical datasets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 μg/mL) and macrosphelide A (4, MIC 75 μg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis.
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影响因子：
5.1
作者：
El-Elimat T;Figueroa M;Ehrmann BM;Cech NB;Pearce CJ;Oberlies NH
通讯作者：
Oberlies NH
影响因子：
2.4
作者：
Martens, Harald;Bruun, Susanne W.;Kohler, Achim
通讯作者：
Kohler, Achim
影响因子：
4.9
作者：
KAATZ, GW;SEO, SM
通讯作者：
SEO, SM
影响因子：
4.1
作者：
Kulakowski, Daniel M.;Wu, Shi-Biao;Kennelly, Edward J.
通讯作者：
Kennelly, Edward J.
影响因子：
3.4
作者：
Inui, Taichi;Wang, Yuehong;Pro, Samuel M.;Franzblau, Scott G.;Pauli, Guido F.
通讯作者：
Pauli, Guido F.