Natural products in modern life science

Abstract

With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure-activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science.

Fig. 1

Explanatory model the interdisciplinary nature of pharmacognosy interpreted in an explanatory model presented by Larsson and co-workers (2008). In this model a clearly defined role is presented for aspects of informatics, including bio- and chemoinformatics. Figure by Sonny Larsson, copyright Phytochemistry Letters, reproduced with permission

Fig. 2

Geodia reef picture taken by remote operated vehicle at 120 m depth showing fouling-free marine sponges of the species Geodia barretti and G. macandrevia living in the Koster Fjord at the Swedish West-coast. Photo by Thomas Lundälv, Tjärnö Marine Biology Laboratory, Sweden, used with permission

Fig. 3

Structures compilation of structures of barettin (1), dipodazine (5) and 13 analogues synthesized and tested by Sjögren and co-workers (2006)

Fig. 4

Phylogeny of fungi phylogeny of asco- and basidiomycetes with focus on taxa with hypogeous fruiting bodies, truffles, based on a combination of several published studies (Læssøe and Hansen ; Hibbet et al. 2007; Celio et al. 2006). Taxa labeled in blue with ∙ indicate evolutionary groups that have developed truffles. The most well known truffle-producing family, Tuberaceae, comprising the edible white and Burgundy truffles is further emphasized in bold lettering. Figure by Christina Wedén and Anders Backlund

Fig. 5

Section of truffle the characteristic scent of the Burgundy truffle does not develop until the entire spore mass has matured, indicating a sophisticated chemical control mechanism. In the picture above we see a fruit body of the truffle Tuber aestivum from the island of Gotland with completely matured spores, showing the interior with a characteristic marbled brown gleba. Photo by Erika Lidén ^©2009, used with permission

Fig. 6

Cyclotide structure. The figure shows a ribbon representation of the crystal structure of varv peptide F (pdbcode 3E4H). Note the seamless peptide backbone and the three disulfides bonds (in yellow) that form the cystine knot: CysI–CysIV, II–V, III–VI. The six loops are marked with roman numerals. Figure by Ulf Göransson

Fig. 7

Comparison of chemical space plots (three subfigures) comparing chemical space coverage from three datasets, a 49,554 compounds screened in the pyruvate kinase assay [grey], b 20,434 compounds from the ZINC-NP subset [magenta], and c 178,210 compounds from WOMBAT 2007.1 corresponding to substances with demonstrated biological activity [lime]. Red axis = PC1, corresponding to size parameters, yellow axis = PC2, corresponding to aromaticity and conjugation related parameters, and green axis = PC3, corresponding mainly to lipophilicity. Figure by Anders Backlund, all predictions scores calculated using ChemGPS-NPweb, plotted using Apple MacOS X bundled software Grapher 2.1

Fig. 8

Chemical space plot of COX inhibitors chemical property space plot of 242 natural products with experimentally demonstrated cox-inhibitory effects. Red axis = PC1, corresponding to size parameters, yellow axis = PC2, corresponding to aromaticity and conjugation related parameters, and pink axis = PC8, corresponding primarily to the Lipinski alert index (LAI), positive values indicating Lipinski ‘rule of five’ violation. Note significant variation in size, and large proportion of compounds with positive LAI values. Picture by Anders Backlund, all predictions scores calculated using ChemGPS-NPweb, plotted using Apple MacOS X bundled software Grapher 2.1, data compiled by Maria Schröder-Vilar

Fig. 9

Pathways predicted metabolic pathways of Entamoeba histolytica based on analysis of its genome showing inferred LGT (3). Glycolysis and fermentation are the major energy generation pathways. Bold gray arrows represent enzymes encoded by genes that are among the 68 candidates for HGT into the Entamoeba histolytica genome. Broken arrows indicate enzymes for which no gene could be identified from the genome data, although the activity is thought to be present. The framed arrow points to the target of Metronidazole, the major drug for treatment of amoebic liver abscess. Abbreviations: PEP phosphoenolpyruvate, GlcNAc N-acetylglucosamine, LCFA long chain fatty acid, VLCFA very long chain fatty acid, PRPP phosphoribosyl pyrophosphate, GPI glycosylphosphatidylinositol, PAPS phosphoadenosine phosphosulfate. [reproduced from previous publication, permission requested]

Fig. 10

Piecharts functional categories among Trichomonas vaginalis and Entamoeba histolytica candidate LGTs. Distribution of functional annotation from the KEGG database among candidate LGTs. [reproduced from previous publication, permission requested]