Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus.
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.
['Palma Esposito|Fortunato|F|0000-0002-3768-4712', 'Giugliano|Rosa|R|0000-0001-9923-3194', 'Della Sala|Gerardo|G|0000-0001-8957-3259', 'Vitale|Giovanni Andrea|GA|', 'Buonocore|Carmine|C|0000-0002-8327-954X', 'Ausuri|Janardhan|J|0000-0002-2017-7482', 'Galasso|Christian|C|0000-0002-1262-959X', 'Coppola|Daniela|D|0000-0001-6699-8967', 'Franci|Gianluigi|G|0000-0003-3321-4331', 'Galdiero|Massimiliano|M|0000-0002-1576-6290', 'de Pascale|Donatella|D|']
D000818:Animals D000998:Antiviral Agents D002522:Chlorocebus aethiops D046508:Culture Techniques D004354:Drug Screening Assays, Antitumor D004952:Esters D016680:Genome, Bacterial D006017:Glycolipids D006801:Humans D055442:Metabolome D008826:Microbial Sensitivity Tests D015394:Molecular Structure D000078722:PC-3 Cells D012240:Rhodococcus D013386:Succinates D013501:Surface-Active Agents D014709:Vero Cells
OSMAC approach metabolomics glycolipids antiviral mass spectrometry antiproliferative biosurfactant marine bacteria microbial natural products trehalolipids