Structure and properties of natural products

WP2: From analytical tools to biological hits

Nature evolution has produced a plethora of metabolic pathways[1] which all influence each other during biological processes. Chemical diversity arises from the functionalization, often at an extreme level of complexity, of important precursors in all natural product series. The combinatorial implementations of these functionalizations lead to huge chemical diversity and thus various biological effects. The description of this chemical and biological diversity – which imposes efforts for metabolic profiling, isolation and structural determination, and biological screening of natural products – paves the way to the comprehension of natural phenomena when couple to omic studies of their biological effects (transcriptomic, proteomic, metabolomic…).

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An integrative view of natural product chemistry © Bastien Nay

Although isolation and structure determination tasks have been well improved thanks to technological achievements, now allowing the identification of minor components from complex biological matters, further developments are still needed to save time and efforts. It may come from the integration of methods, or hyphenation in analytical chemistry. Hyphenation refers to as the online coupling of analytical methods from compound separation to their full analysis, sometimes up to biological screening. It is thus possible to couple HPLC separation with NMR and MS analysis, followed by in vitro detection of biological properties.[2]

cropped-image52.pngFinally, echoing the objectives of WP1, a chemical inventory of biodiversity is qualitatively and quantitatively needed to understand the interactions of species, including complex molecular mechanisms. Qualitatively, the access to structural identity goes far beyond the molecular topology of compounds. Indeed by reading inside structures and their diversity, it is possible to envision the complexity of metabolic pathways and predict biosynthetic events, up to gene expression and regulatory pathways. The molecular diversity profile produced by living organisms depends on the environmental conditions directly connected to these regulatory pathways. Quantitatively, metabolic profiling and data analysis performed through metabolomics, along with gene expression analyzed by transcriptomics, allow global approaches of natural products to be undertaken. In that sense, WP2 connects WP1 to the biosynthetic matter of WP3.

[1] See for example the KEGG Pathway Database.

[2] N. Bohni, M. L. Cordero-Maldonado, J. Maes, D. Siverio-Mota, L. Marcourt, S. Munck, A. R. Kamuhabwa, M. J. Moshi, C. V. Esguerra, P. A. M. de Witte, Al. D. Crawford, J.-L. Wolfender, PlosOne 2013, 8, e64006.

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