Nature has developed an enormous biodiversity during several billion years of evolution. The biological species coexist in ecosystems and interact with each other in several ways in which chemistry plays a major role – for example, in defence and symbiosis. In basic terms, these organisms share a similar biochemistry (defined by primary metabolites such as amino acids, fatty acids and nucleotides), but, in addition, some micro- and macroorganisms produce a wide variety of "secondary metabolites" giving them an evolutionary advantage in their interactions with the environment. Considering the number of organisms, and the almost infinite number of interactions possible, it is not surprising that an enormously wide variety of metabolites, with a large variance in chemical structures and properties, has evolved within organisms (chemical diversity from biodiversity).
The principal focus of our research activities relies on the use of the modern methods of organic chemistry for understanding and solving problems lying at the interface between chemistry and other fundamental disciplines such as biology and physics. In particular our research, broadly named “Natural Product Chemistry”, requires a strongly interdisciplinary approach affording both basic information and new products and a wider view towards any chemical aspect of biodiversity (metabolomics). Our research activities are mainly related to 3 general aspects:
- From biological to chemical diversity: structural characterization of new natural products and their exploitation in drug discovery projects. Once biological extracts have been obtained from a natural source, the chemical structures of the active constituents have to be elucidated. The detailed structural information of isolated metabolites, carried out by using the most advanced Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques, still represent a condito sine qua non for their biotechnological exploitation. Biological screenings and the creation of libraries of purified and identified natural products (proprietary database). can thus compete directly with synthetic libraries in drug discovery/development strategies.
- From chemical diversity to metabolomics : analysis of cell’s lipids composition. Lipids are of crucial importance for basic cell functions such as cell trafficking and signal transduction. Fingerprinting' techniques are used for rapid profiling and specific chemical information. Samples are examined after solvent extraction, or as intact tissues (magic angle spinning NMR), liquids or semi-solids (multinuclear NMR, advanced LC-ESI-MS techniques), or dried materials (FT-IR). The aim of this approach (metabolomics) is to obtain the widest possible coverage, in terms of the type and number of compounds analyzed; in particular, we are now strongly interested in the role played by membranes lipids in the cold adaptation of psychrophilic microorganisms.
- From metabolomics to biological classification. Since the metabolites production is genetically controlled, they are taken into consideration also for systematic, taxonomic and ecological purposes. Our multidisciplinary approach allows to establish a polyphasic database wherein morphological and genetic information are compared with chemo-diversity as obtained by using general metabolic fingerprinting methods (NMR, MS and IR) from crude extracts or whole organisms.
- Graziano Guella, PI
- Ines Mancini, PhD, Research Associate
- Rita Frassanito, Research Assistant
- Defant Andrea, MD, Research Assistant
- Sferni Adriano, Technical Assistant
- Rossi Mario, Technical Assistant
- Tom Turk and Kristina Sepcic, Dept of Biology, University of Ljubljana, Slovenia
- Roderick Scott, College of Medical Sciences, University of Aberdeen, Scotland, U.K.
- Cecile Debitus, Université Paul Sabatier Toulouse III, France
- Fernando Dini and Paola Bagnoli, Dept. of Biology, University of Pisa, Italy
- Mauro Dalla Serra, Istituto Biofisica CNR, Trento, Italy
- Marco Cantonati and Valeria Lencioni, Museo Tridentino Scienze Naturali, Trento,Italy
- Giovanna Flaim and Fulvio Mattivi, Fondazione Mach San Michele, Trento, Italy
- Alessandro Bagno, Dept. of Chemistry, University of Padova, Italy
Guella G, Callone E, Di Giuseppe G, Frassanito R, Frontini F, Mancini I, Dini F. 2007. Hemivannusal and prevannusadials, new sesquiterpenoids from the marine ciliate protist, Euplotes vannus: the putative biogenetic precursors of vannusals dimeric terpenoids. Eur J Org Chem, in press.
Cervia D, Garcia-Gil M, Simonetti E, Di Giuseppe G, Guella G, Bagnoli P, Dini F. 2007. Molecular mechanisms of euplotin C-induced apoptosis: involvement of mitochondrial dysfunction, oxidative stress and proteases. Apoptosis 12: 1349-1363.
Mancini I, Defant A, Guella G. 2007 Recent synthesis of marine natural products with antibacterial activities. Anti-infective Agents Med Chem 6: 17-48.
Mancini I, Guella G, Frostin M, Hnawia E, Laurent D, Debitus C, Pietra F. 2006. On the first polyarsenic organic compound from nature: arsenicin A from the New Caledonian marine sponge Echinochalina bargibanti. Chem Eur J 12: 8989-8994.
Drechsler A, Sabo J, Potrich C, Frisanco M, Guella G, Dalla Serra M, Anderluh G, Separovic F, Norton RS. 2006. Structure and activity of the N-terminal region of the eukaryotic cytolysin equinatoxin II. Biochemistry 45: 1818-1828.
Frassanito R, Flaim G, Mancini I, Guella G. 2006. High production of unexpected carotenoids in Dinophyceae. Astaxanthin-esters of the freshwater dinoflagellate Tovellia sanguinea. Biochem Syst Ecol 34: 843-853.
Frassanito R, Cantonati M, Tardìo M, Mancini I, Guella G. 2005. On-line identification of secondary metabolites in freshwater microalgae and cyanobacteria by combined liquid chromatography–photodiode array detection-mass spectrometric techniques. J Chromatogr A 1082: 33-42.
Mancini I, Sicurelli A, Guella G, Turk T, Macek P, Sepcic K. 2004. Synthesis and bioactivity of linear oligomers related to polymeric alkylpyridinium metabolites from the Mediterranean sponge Reniera sarai. Org Biomol Chem 2: 1368-1375.
Anderluh G, Dalla Serra M, Viero G, Guella G, Macek P, Minestrina G. 2003. Pore formation by equinatoxin II, a eukaryotic protein toxin, occurs by induction of nonlamellar lipid structures. J Biol Chem 278: 45216-45223.
Guella G, Frassanito R, Mancini I. 2003. A new solution for an old problem: the regiochemical distribution of the acyl chains in galactolipids can be established by electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 17: 1892-1994.