The rapid innovations in metabolite profiling, bioassays and chemometrics lead to a paradigm shift in natural product (NP) research. Indeed, having at hand partial/full structure information of possibly all secondary metabolites and an estimation of their levels in plants, provides a way to perform pharmacognostic investigations from a new and holistic perspective. The increasing amount of accurate metabolome data that can be acquired on massive sample sets, notably through data dependent HRMS/MS, allows mapping natural extracts at an unprecedented precision level [1,2]. In this context, data contextualization is however still a lagging process [3].
For this, we investigated methods that could provide enhanced annotation confidence level through multiple scores integrating taxonomy information and molecular network (MN) structural consistency as well as other orthogonal analytical data. Benchmarking of such approaches is currently assessed by profiling mixtures of herbs with well-studied composition. We also investigate the best way to integrate extracts bioactivity data in MN and shortcut bioactivity guided isolation for an efficient targeted identification of bioactive NPs [4]. To this end, accurate chromatography gradient methods at various scales have been developed for MS-targeted purification of biomarkers and their full de novo structure identification by NMR.
Different recent applications of our metabolomics/phytochemical investigations will illustrate these aspects. Evaluation of what is readily implemented and is still required in NP research will be made, notably in terms of contextualisation of the data.
Keywords : Dereplication, metabolite profiling, metabolomics, MS-targeted isolation
References:
[1] Wolfender J-L et al. J Chromatogr A 2015 1382: 136-164.
[2] Allard PM et al. Anal. Chem. 2016 88: 3317-23.
[3] Allard, P.-M. et al. Curr. Opin. Biotechnol. 2018, 54, 57-64.
[4] Olivon, F., et al. ACS Chem Biol 2017, 12, 2644-2651.