Molecular Networking to target the isolation of novel isoprenoids derivatives from marine-derived actinomycetes

Marine-derived actinobacteria have been considered a rich source of new and complex chemical structures with a large range of pharmacological and biotechnological properties. However, the dereplication process, a major bottleneck in Natural Products (NP) discovery,1 is an extremely important step in this type of studies to discard known compounds and accelerate the isolation and characterization of new chemical structures. In this context, Molecular Networking2 has been used to develop the world's largest repository of MS/MS data and an online tool for data analysis is available at https://gnps.ucsd.edu/, named Global Natural Products Social Molecular Networking (GNPS). It uses fragmentation data obtained from mass spectrometry to cluster chemical compounds by structural similarity. This tool has accelerated the chemical content identification in NP studies, allowing the fast analysis of a great amount of samples and guiding the isolation of new compounds. In this work, we have applied mass spectrometry approaches and molecular networking to investigate the chemical content of crude extracts produced by actinomycetes phylogenetically related to Streptomyces aculeolatus that were obtained from marine sediments collected off the Madeira Archipelago,3 Figure 1.

Fig. 1. Schematic workflow of the methodology.

The approach used in our work allowed for the identification of new compounds, including hybrid isoprenoids derivatives, which have been described as potent antibiotic and anticancer compounds.

Figure 1
Image
Acknowledgements
FCT, through grants PTDC/QUIQUI/119116/2010, PTDC/FIS-NAN/0117/2014, IF/00700/2014, UID/Multi/04378/2013 (UCIBIO), UID/QUI/ 50006/2013 (LAQV) and co-financed by the FEDER under the PT2020 partnership agreement POCI-01-0145-FEDER-007728 and POCI-01-0145-FEDER-007265. The NMR spectrometers are part of The National NMR Facility, supported by FCT (RECI/BBB-BQB/0230/2012). The EU 7th Framework Programme (FP7/2007–2013) under grant agreement PCOFUND-GA- 2009-246542. FAPESP process 2017/1717648-4.

References
1. Gaudencio, S.P., and Pereira, F. (2015) Dereplication: racing to speed up the natural products discovery process. Natural Product Reports 32: 779-810.
2. Wang, M.X., Carver, J.J., Phelan, V.V., Sanchez, L.M., Garg, N., Peng, Y. et al. (2016) Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology 34: 828-837.
3. Prieto-Davo, A., Dias, T., Gomes, S.E., Rodrigues, S., Parera-Valadezl, Y., Borralho, P.M. et al. (2016) The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential. Frontiers in Microbiology 7.