Genome-based natural product discovery: Characterization of bioactive compounds in marine Actinobacteria

Natural compounds represent the best starting point for the development of new drugs with novel mechanisms of action. Especially actinomycetes, which are gram-positive bacteria, continue to be a renowned source of natural products, due to their ability to produce a myriad of structurally-rich bioactive compounds. Many of the naturally-occurring compounds derived from marine actinomycetes possess unique structural characteristics not found among compounds isolated from terrestrial sources. However, traditional approaches towards identification of new antibiotic biosynthetic pathways and products are rather time consuming and are no longer suffice. Also, expertise of research groups is generally in one defined field of the whole pipeline of bioactivity-guided isolation for natural product drug discovery.

Within this project we identify and experimentally characterize unique anti-microbial compounds from biosynthetic genes encoding non-ribosomal peptide synthetases (NRPS) in unique marine habitats. We develop synergic pipeline involving the collection of sediment samples till the synthesis of bioactive compounds (focus on peptides) with novel mode of action.

This project embraces a suite of cutting-edge methods of microbiology, molecular biology, analytical chemistry, bioinformatics, and peptide-/ organic chemistry to answer interdisciplinary groundbreaking questions: Do environmental regimes (by analyzing sediments from Chile) influence actinomycetes antimicrobial compound production? What is the ratio of identified compounds of peptide or small molecule origin? Can novel posttranslational modifications be found in compounds isolated? Can compounds be identified targeting selectively gram-positive or gram-negative bacteria? Finally, we contribute to antimicrobial research with the basic knowledge generated from results of this project by combining unique expertise of international collaborative research.

The principle participants in this project are: Alesia A. Tietze (project responsible, Department of Chemistry and Molecular Biology, UGOT, Wallenberg Centre for Molecular and Translational Medicine) LINK TO: www.tietze-lab.com, Beatriz Camara (Universidad Técnica Federico Santa María in Valparaiso, Chile), Roger Karlsson (Clinical microbiology, Sahlgrenska University Hospital, UGOT), Carl-Johan Wallentin (Department of Chemistry and Molecular Biology, UGOT), Edward Moore (Head Curator for the GU Culture Collection) LINK TO: www.ccug.se,