PhD Project 3

Exploitation of a collection of marine-derived microbial extracts as source of new antibiotics useful in human, plant, and fish infections

Georgia Karyofyllidou

I am currently a PhD fellow at Fundación MEDINA in Granada, Spain. I am holding a bachelor’s degree in biology from Aristotle University of Thessaloniki followed by a master’s degree in chemistry of Natural Products from National & Kapodistrian University of Athens, Greece. My PhD thesis is focused on the exploration of marine natural products for the discovery of new natural antibiotics. This research starts with the screening of a collection of marine microbial strains, which are already available at Fundación MEDINA and have been generated through the One Strain Many Compounds (OSMAC) approach. Through systematic screening of microbial extracts against various plant, fish and human pathogens and the use of LC/HRMS and LC-MS/MS for compound dereplication, the project seeks to isolate, identify, and elucidate the structure of novel bioactive molecules.

Exploitation of a collection of marine-derived microbial extracts as source of new antibiotics useful in human, plant, and fish infections

A collection of microbial extracts from ~200 marine derived strains already available at MEDINA, generated using a One Strain Many Compounds (OSMAC) approach by growing each strain in 5 different selected culture media will be used as starting point for:

1) Testing of this extract collection against human, plant and fish pathogens.

2) Dereplication of the best bioactive hits using LC-HRMS and LC-MS/MS analyses combined with the use of internal spectral databases, the Dictionary of Natural Products (DNP) and the Global Natural Products Social Molecular Networking (GNPS) and selection of the best candidates for fractionation.

3) Scaled-up fermentation, extraction, and fractionation of best candidates (3-30 L) for the purification of the bioactive molecules.

4) Structural elucidation of new molecules obtained using HRMS and NMR techniques.

5) Full profiling of the bioactive compounds against an extended panel of pathogens and other assays available from different consortium partners as well ADME-Tox assessment of the new molecules.

6) Genome mining of the strains yielding the most interesting candidates to identify the biosynthetic gene clusters (BGC) responsible for their production.

Supervisors: Fernando Reyes and Olga Genilloud

Host institution: Fundación MEDINA

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