Towards an efficient and targeted isolation of valuable natural products only

With the recent progresses made in metabolite profiling methods and miniaturization of bioassays, a question that arises is: do we still need to perform conventional large scale bioactivity-guided isolation of natural products (NPs)? High resolution mass spectrometry (HRMS) and data dependent MS/MS analyses provide very valuable information on secondary metabolites for in-depth metabolome annotation studies [1]. The recent development of molecular network (MN) approaches for the mining of such data gives the possibility to establish relationships between metabolites, thus significantly improving the efficiency of dereplication, particularly when combined with high quality chemotaxonomic data [2]. Such types of information can be generated with a few mg of extract only and are readily applicable to herbarium scale samples. For complete de novo identification of new compounds MS-targeted micro-isolation can be performed, and sensitive 1D and 2D microNMR data can be acquired with microgram amounts of purified metabolites. For bioactivity determination, many bioassays also fit to this scale. Using an ideal combination of methods, it is thus virtually possible to fully identify any bioactive principles in this way. Integration of other filters to this approach such as permeation studies on extracts additionally provide key information on the possible bioavailability of NPs prior to their isolation [3]. Furthermore the link of a given bioactivity result to those previously reported for compounds similar to those identified can be rationalised through in silico chemical space approaches. Ideally, a combination all these state-of-the-art methods should enable to identify and localise valuable NPs efficiently at the analytical scale. In such a way large scale MS-targeted isolation of valuable NPs only can become a very rational way to conduct investigations.

Keyword: Dereplication, metabolite profiling, permeation, MS-targeted isolation.

References:

[1] Wolfender J-L, Marti G, Thomas A, Bertrand S. Current approaches and challenges for the metabolite profiling of complex natural extracts. J Chromatogr A 2015; 1382: 136 – 164

[2] Allard P-M, Péresse T, Bisson J, Gindro K, Marcourt L, Pham VC, Roussi F, Litaudon M, Wolfender J-L. Integration of molecular networking and in-silico MS/MS fragmentation for natural products dereplication. Anal Chem 2016; 88: 317 – 3323

[3] Petit C, Bujard A, Skalicka-Woźniak K, Cretton S, Houriet J, Christen P, Carrupt PA, Wolfender JL. High-throughput prediction of passive intestinal absorption of natural products and plant extracts with the PAMPA assay. Planta Med 2015; 81: SL1A_03