Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus.

Fortunato Palma Esposito,Carmine Buonocore,Rosa Giugliano,Donatella De Pascale,Gerardo Della Sala,Giovanni Andrea Vitale,Gianluigi Franci,Daniela Coppola,Janardhan Ausuri,Christian Galasso,Massimiliano Galdiero

doi:10.3390/ijms22169055

Abstract

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.

Highlights

IntroductionNatural products (NPs) of microbial origin, mainly from soil bacteria, have inspired most of our common commercial pharmaceuticals
These results clearly indicate that the F90 antiviral activity is always higher results clearly indicate that the F90 antiviral activity is always higher than that exerted by than that exerted by the crude extract, suggesting this fracthe crude extract, suggesting this fraction to be enriched of tion to be enriched of antiviral compounds (Figure 6)
Taking into account the high surfactant activity shown by F90 in CTAB assay (Figure 8b), these findings suggest that the antiviral action is likely due to a physicochemical interaction of biosurfactant compounds with the virus lipid membrane leading to envelope damage

Summary

Introduction

Natural products (NPs) of microbial origin, mainly from soil bacteria, have inspired most of our common commercial pharmaceuticals. A shift in focus, from the terrestrial to the marine environment, resulted in the discovery of a wide variety of new industrially relevant metabolites [1]. One of the main barriers is represented by the high rediscovery rate of already known metabolites, turning the drug discovery process into a waste of resources [2]. New progresses have been made to overcome these issues, prioritizing the use of talented strains. Recent advances in microbial DNA sequencing technologies allow whole genome sequencing in a rapid and cost-effective way

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