A research pipeline for the discovery of bioactive small molecules with healthy ageing-promoting activity from the marine mesophotic zone
Eleni-Dimitra Papanagnou 1, Nikolas Fokialakis 2, Maria-Christina Cheimonidi 1, Eirini Baira 2, Géraldine Le Goff 3, Pinelopi Vlachou 2, Nikolaos Tsafantakis 2, Pedro Álvarez 4, Suchana Chavanich 5, Anne Bialecki 6, Yehuda Benayahu 7, Christine Wenzkowski 8, Jamal Ouazzani 3, Ioannis P. Trougakos 1
1 Faculty of Biology, National & Kapodistrian University of Athens, Athens, Greece
2 Faculty of Pharmacy, National & Kapodistrian University of Athens, Athens, Greece
3 ICSN-CNRS, Gif sur Yvette, France
4 iMare Natural, Granada, Spain
5 Chulalongkorn University, Bangkok, Thailand
6 Université de la Réunion, Ile de la Réunion, France
7 Tel Aviv University, Tel Aviv, Israel
8 Crelux GmbH, Martinsried, Germany
In the frame of TASCMAR, marine invertebrate species (MACLIB and TARMAC libraries) were collected from the mesophotic zone (between 30 and 100 meters depth) of the Indian ocean, the Red sea and the Mediterranean. Furthermore, associated microorganisms of MACLIB and TARMAC libraries respectively, were collected (MICLIB and TARMIC libraries). The samples were extracted and libraries of extracts were sent for biological evaluation; i.e. elastase, tyrosinase, proteasome, Fyn and CDK7 kinase inhibitory activity assays. All active extracts were investigated for their chemical profiling employing UHPLC-HRMS techniques
and the metabolites present in each extract were identified using molecular networks, in silico fragmentation and classical dereplication techniques based on databases. Selected extracts were fractionated and a library of fractions has been forwarded for bio-evaluation. From the active fractions compounds of interest have been isolated and identified by NMR and LC-MS. Furthermore, the biological activity of the associated microorganisms was examined. Finally a comparison between the LC-MS profiles of the invertebrate extracts and the profiles of the microbial symbionts was performed showing overlapping of 4 to14% indicating the contribution of microorganisms to the whole invertebrate metabolome.
Conflict of interest: The authors declare no conflict of interest.
Acknowledgement: We acknowledge the Special Account for Research Grants of NKUA, Greece for funding.
1 Faculty of Biology, National & Kapodistrian University of Athens, Athens, Greece
2 Faculty of Pharmacy, National & Kapodistrian University of Athens, Athens, Greece
3 ICSN-CNRS, Gif sur Yvette, France
4 iMare Natural, Granada, Spain
5 Chulalongkorn University, Bangkok, Thailand
6 Université de la Réunion, Ile de la Réunion, France
7 Tel Aviv University, Tel Aviv, Israel
8 Crelux GmbH, Martinsried, Germany
In the frame of TASCMAR, marine invertebrate species (MACLIB and TARMAC libraries) were collected from the mesophotic zone (between 30 and 100 meters depth) of the Indian ocean, the Red sea and the Mediterranean. Furthermore, associated microorganisms of MACLIB and TARMAC libraries respectively, were collected (MICLIB and TARMIC libraries). The samples were extracted and libraries of extracts were sent for biological evaluation; i.e. elastase, tyrosinase, proteasome, Fyn and CDK7 kinase inhibitory activity assays. All active extracts were investigated for their chemical profiling employing UHPLC-HRMS techniques
and the metabolites present in each extract were identified using molecular networks, in silico fragmentation and classical dereplication techniques based on databases. Selected extracts were fractionated and a library of fractions has been forwarded for bio-evaluation. From the active fractions compounds of interest have been isolated and identified by NMR and LC-MS. Furthermore, the biological activity of the associated microorganisms was examined. Finally a comparison between the LC-MS profiles of the invertebrate extracts and the profiles of the microbial symbionts was performed showing overlapping of 4 to14% indicating the contribution of microorganisms to the whole invertebrate metabolome.
Conflict of interest: The authors declare no conflict of interest.
Acknowledgement: We acknowledge the Special Account for Research Grants of NKUA, Greece for funding.
