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Natural compounds are evolutionary selected and pre-validated by Nature, displaying a unique diversity of chemical properties and corresponding biological activities. Of utmost importance for a rational discovery and exploration of new biologically active compounds are two aspects: one the identification and charting of the biologically relevant chemical space, the other a similar charting of the corresponding evolutionary space [1 pro parte].
he first key to this is the coverage of the natural products' chemical space. For this purpose we introduced ChemGPS-NP [2, 3], with the aim to provide a tool for more efficient and stringent compound comparison, to identify parts of chemical space related to particular biological activities, and to track changes in chemical properties due to e.g. evolutionary traits and modifications in biosynthesis. Physical-chemical properties not directly discernible from structural data can be compared, making selection more rational when screening natural compounds and analogues.
The second key would consequently be to explore evolutionary space by elucidating and utilising robust phylogenies for the organisms under study. From this basis reflecting the evolutionary history and hence biosynthesis development, further conclusions can be drawn [e.g. 4, 5].
Based these initial attempts, the intersection of chemical and evolutionary space have been explored. With regard to e.g. compound classes such as iridoids, betalains, and sesquiterpene lactones, evolutionary patterns of changes in physical-chemical properties are observed and compared. For eight major classes of plant defence peptides analyses of structure base alignments provide arguments for rational classification. In addition, evolution of the enzyme Rubisco, have been explored with reference to major structural features.
References: 1. Bohlin, L. et al. (2007) Pure Appl. Chem. 79:763–774.
2. Larsson, J. et al. (2005)J. Nat. Prod. 68:985–991.
3. Larsson, J. et al. (2007)J. Nat. Prod. 70:789–794.
4. el-Seedi, H, et al. (2005) Biochem. Syst. Ecol. 33:831–39.
5. Andersson, I., Backlund, A. (2008) Plant Phys. Biochem. 46:275–291.