MixONat, a Software for the Dereplication of Mixtures Based on 13C NMR Spectroscopy
MixONat, a Software for the Dereplication of Mixtures Based on 13C NMR Spectroscopy
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DOI：
10.1021/acs.analchem.0c00193
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发表时间：
2020-07-07
影响因子：
7.4
通讯作者：
Richomme, Pascal
中科院分区：
文献类型：
--
作者：
Bruguiere, Antoine;Derbre, Severine;Richomme, Pascal
无论是化学家还是生物学家，研究代谢组学的研究人员都需要工具来破译复杂的混合物。作为代谢组学的一部分，最初致力于鉴定生物活性天然产物，反重复旨在减少已知化合物分离通常耗时的过程。质谱和核磁共振是在重复分析中最常用的分析工具。虽然C-13核磁共振的灵敏度较低，但它在这类研究中有很多优势。值得注意的是，它是非特异性的，允许同时高分辨率分析任何有机化合物，包括立体异构体。由于核磁共振光谱仪如今在合理的时间框架内提供有用的数据集，我们已经着手编写专门用于C-13核磁共振去复制的软件。本研究描述了一个自由分布算法的发展，即MixONat及其帮助研究人员破译复杂混合物的能力。MixONat基于Python 3.5分析{H-1}-(BC)- b -13核磁共振谱，可选择结合DEPT-135和90数据，以区分碳类型（即CH3， CH2， CH和C），以及MW过滤。该软件需要预测或实验碳化学位移（δ c）数据库，并显示可根据用户交互改进的结果。作为概念验证，该C-13 NMR反复制策略在日益复杂的混合物中进行了评估，并展示了药物（罂粟生物碱），营养（迷迭香提取物）或化妆品（山竹皮提取物）的应用。将相关结果与其他常用的去重复方法进行比较。MixONat给出了一致的结果，迅速将用户导向二级代谢物的正确结构类型，允许用户区分结构接近的天然产物，包括立体异构体。
Whether chemists or biologists, researchers dealing with metabolomics require tools to decipher complex mixtures. As a part of metabolomics and initially dedicated to identifying bioactive natural products, dereplication aims at reducing the usual time-consuming process of known compounds isolation. Mass spectrometry and nuclear magnetic resonance are the most commonly reported analytical tools during dereplication analysis. Though it has low sensitivity, C-13 NMR has many advantages for such a study. Notably, it is nonspecific allowing simultaneous high-resolution analysis of any organic compounds including stereoisomers. Since NMR spectrometers nowadays provide useful data sets in a reasonable time frame, we have embarked upon writing software dedicated to C-13 NMR dereplication. The present study describes the development of a freely distributed algorithm, namely MixONat and its ability to help researchers decipher complex mixtures. Based on Python 3.5, MixONat analyses a {H-1}-(BC)-B-13 NMR spectrum optionally combined with DEPT-135 and 90 data-to distinguish carbon types (i.e., CH3, CH2, CH, and C)-as well as a MW filtering. The software requires predicted or experimental carbon chemical shifts (delta c) databases and displays results that can be refined based on user interactions. As a proof of concept, this C-13 NMR dereplication strategy was evaluated on mixtures of increasing complexity and exhibiting pharmaceutical (poppy alkaloids), nutritional (rosemary extracts) or cosmetics (mangosteen peel extract) applications. Associated results were compared with other methods commonly used for dereplication. MixONat gave coherent results that rapidly oriented the user toward the correct structural types of secondary metabolites, allowing the user to distinguish between structurally close natural products, including stereoisomers.