Time Dependency of Chemodiversity and Biosynthetic Pathways: An LC-MS Metabolomic Study of Marine-Sourced Penicillium.

Catherine Roullier,Thibaut Robiou Du Pont,Olivier Grovel,Yann Guitton,Yves Pouchus,Samuel Bertrand,Elodie Blanchet,Mathilde Peigné

doi:10.3390/md14050103

Abstract

This work aimed at studying metabolome variations of marine fungal strains along their growth to highlight the importance of the parameter “time” for new natural products discovery. An untargeted time-scale metabolomic study has been performed on two different marine-derived Penicillium strains. They were cultivated for 18 days and their crude extracts were analyzed by HPLC-DAD-HRMS (High Performance Liquid Chromatography-Diode Array Detector-High Resolution Mass Spectrometry) each day. With the example of griseofulvin biosynthesis, a pathway shared by both strains, this work provides a new approach to study biosynthetic pathway regulations, which could be applied to other metabolites and more particularly new ones. Moreover, the results of this study emphasize the interest of such an approach for the discovery of new chemical entities. In particular, at every harvesting time, previously undetected features were observed in the LC-MS (Liquid Chromatography-Mass Spectrometry) data. Therefore, harvesting times for metabolite extraction should be performed at different time points to access the hidden metabolome.

Highlights

It is generally admitted that only a small part of the marine fungal metabolic potential is observed under classical experiments consisting in cultivating one strain in axenic conditions on a common medium over a definite period of time
The mycelium spreads in all directions from the seeding point, due to a highly polarized process of hyphal tip extension, and forms typical circular colonies, which diameter can be followed through time to assess the fungal growth [41,42,43]
Two Penicillium strains were cultivated over an 18 days period

Summary

Introduction

It is generally admitted that only a small part of the marine fungal metabolic potential is observed under classical experiments consisting in cultivating one strain in axenic conditions on a common medium over a definite period of time. This greatly limits the potential of drug discovery from fungi [1]. To overcome this issue, many research teams have investigated ways to unravel cryptic biosynthetic pathways to access a wider chemodiversity [2,3,4].

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Conclusion