Research in QOSBio involves different projects, including biodiscovery of bioactive natural products, biosynthesis of microbial secondary metabolites, investigating the chemistry of microbe-holobionts associations as well as collaborative projects in synthesis and medicinal chemistry.
Biodiscovery of New Bioactive Secondary Metabolites
Secondary metabolites produced and accumulated by micro- and macro-organisms represent a treasure for the discovery of novel bioactive chemical entities. During several years the group has devoted efforts towards the discovery of natural products from marine sponges, ascidians, nudibranchs, bryozoans, fungi and, more recently, produced by bacteria. Research include marine invertebrate collections at different locations of the Brazilian coastline, in a team of researchers currently involving Professores Eduardo Hajdu (Museu Nacional-UFRJ), Rosana M. Rocha (IB-UFRJ), Vinícius Padula (Museu Nacional-UFRJ), Leandro M. Vieira (CCB-UFPE). Collections are also performed in the São Sebastião region (São Paulo state), where is located the Centro de Biologia Marinha of Universidade de São Paulo.
Isolation of bacteria and fungi are developed in collaboration with research groups of Professor Fabiano L. Thompson (IB-UFRJ), Professor Simone P. Lira (ESALQ-USP) and Professor André Rodrigues (IB-UNESP-Rio Claro). Past collaboration with Professor Lara D. Sette in marine fungi metabolism is still ongoing.
Essential in biodiscovery programs are collaborations with well established groups developing relevant bioassays. These include Dr. Andréa Dessen (Bacterial Pathogenesis Group, Institut de Biologie Structurale, Université Grenoble Alpes), Dr. Daniela Trivella (LNBio-CNPEM), Dr. Raquel Alves dos Santos (UniFran), Dr. Carlos Henrique Gomes Martins (UniFran), Professor Danilo Ciccone Miguel (IB-UNICAMP), Professor Fernanda Ramos Gadelha (IB-UNICAMP) and Professor Rafael Guido (IFSC-USP-São Carlos).
Professor Andréa Dessen’s group is interested in studying mechanisms employed by bacteria to initiate infection by tackling a number of different systems: – The bacterial cell wall: macromolecular complexes and antibiotic development targets; – secreted and surface-associated virulence factors ; – bacterial secretion systems: architecture and toxin secretion.
The scientific and technological activities at LNBio are organized into five Thematic Programs, comprising research and development projects in strategic areas of biosciences and biotechnology.
Professor Raquel A. Santos’ group investigates the discovery and mechanism-of-action of anticancer agents. Professor Carlos H. G. Martins’ groups focuses on the research of new anti-bacterial and anti-fungal agents.
Professor Danilo C. Miguel’s group investigates interactions between Leishmania spp. and macrophages, while Professor Fernanda R. Gadelha’s group investigates the biology of the Chagas Disease ethiologic agent, Trypanosoma cruzi.
Professor Rafael Guido’s group focuses on the structural elucidation of relevant molecular targets and the application of this knowledge toward the discovery and development of new drugs and agrochemicals for human and plant diseases.
Methods for the Isolation of Secondary Metabolites
Our group has a major interest in developing approaches towards the isolation of novel natural products. These include compounds present in very complex biological matrixes, minor metabolites and water-soluble compounds. We develop methods for the optimization of metabolite production in order to increase isolation yields [1-5]. We are also interested in exploring unusual isolation strategies, such as adsorptive resins, different gel-filtration stationary phases and HPLC columns suitable for the isolation of water-soluble and/or minor compounds [5-10].
2. Kossuga et al., Evaluating methods for the isolation of marine-derived fungal strains and production of bioactive secondary metabolites. Rev. Braz. Farmacogn. – Braz. J. Pharmacogn., 2012, 22, 257-267.
8. Rodríguez et al., The marine-derived fungus Tinctoporellus sp. CBMAI 1061 degrades the dye Remazol Brilliant Blue R producing anthraquinones and unique tremulane sesquiterpenes. RSC Advances, 2015, 5, 66360-66366.
9. Nicacio et al., Cultures of the Marine Bacterium Pseudovibrio denitrificans Ab134 Produce Bromotyrosine-Derived Alkaloids Previously Only Isolated from Marine Sponges, J. Nat. Prod. 2017, 80, 235−240.
10. Parra et al., Isolation, Derivative Synthesis, and Structure−Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis. J. Nat. Prod. 2018, 81, 188−202.
Structural Investigation of New Natural Products
The correct assignment of new organic compounds from biological sources is often regarded as trivial. Nonetheless, it is much easier to assign a wrong structure than a correct structure for a novel natural product. The correct structure assignment requires high-quality data. Our collaborations in obtaining high-quality NMR data and data analyses include Professor Antonio G. Ferreira (NMR laboratory, Universidade Federal de São Carlos), Professor Raymond J. Andersen (University of British Columbia) and Professor Tadeusz Molinski (Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego).
Biosynthesis of Microbial Natural Products
We seek to investigate and understand how microbial natural products are constructed. We perform investigations using 13C-labeled precursors as well as investigations on the genome, enzymes involved in the biosynthesis and of structural biology. Biosynthesis investigations have been developed in collaboration with Prof. David H. Sherman – Life Sciences Institute, University of Michigan.
Romminger, S.; Pimenta, E. F.; Nascimento, E.S.; Ferreira, A.G.; Berlinck, R.G.S. Biosynthesis of two dihydropyrrole-polyketides from a marine-derived Penicillium citrinum. J. Braz. Chem. Soc., 2012, 23, 1783-1788.
Mercado-Marin, E., Garcia-Reynaga, P., Romminger, S., Pimenta, E. F., Romney, D.,Lodewyk, M., Williams, D. E., Andersen, R. J., Miller, S., Tantillo, D., Berlinck, R. G. S., Sarpong, R. Total synthesis and isolation of citrinalin and cyclopiamine congeners. Nature, 2014, 509, 318–324.
Ferreira, E.L.F., Williams, D.E., Ióca, L.P., Morais-Urano, R.P., Santos, M.F.C., Patrick, B.O. Elias, L.M. Lira, S.P., Ferreira, A.G., Passarini, M.Z.R., Sette, L.D., Andersen, R.J., Berlinck, R.G.S. Structure and Biogenesis of Roussoellatide, a Bis-chlorinated Polyketide from the Marine-Derived Fungus Roussoella sp. DLM33, Organic Letters, 2015, 17, 5152-5155.
Newmister, S. A.; Gober, C. M; Romminger, S.; Yu, F.; Tripathi, A.; Parra, L. L. L.; Williams, R. M.; Berlinck, R. G. S.; Joullié, M. M.; Sherman, D. H.; OxaD: A Versatile Indolic Nitrone Synthase from the Marine-Derived Fungus Penicillium oxalicum F30, Journal of the American Chemical Society. 2016, 138, 11176−11184.
Newmister, S.; Romminger, S.; Schmidt, J. J.; Smith, J. L. L.; Williams, R. M..; Berlinck R. G. S..; Sherman, D. H.; Unveiling sequential late-stage methyltransferase reactions in the meleagrin/oxaline biosynthetic pathway. Organic and Biomolecular Chemistry 2018, advance article.