Marine fungi have been found in all habitats and are able to adapt to their environmental niche con-ditions. In this study, a combination of LC-HRMS and GC-MS analytical approaches was used to analyse the whole metabolic changes of a marine sourced Penicillium restrictum strain isolated from a marine shellfish area. The P. restrictum MMS417 strain was grown on seven different media in-cluding an ecological one with two different water sources (synthetic sea water and distilled water) conditions following the OSMAC approach. Extracts of all media were analysed by LC-HRMS (lipids and specialised metabolites profiling) and GC-MS (fatty acids profiling). Aquired data were analysed using a multiblock strategy to highlight metabolic modification in regards to water condi-tions and to environmentally relevant conditions (mussel-based culture medium). This revealed that fatty acid composition of lipids was the most altered part of the explored metabolisms either looking to water effect and to environmentally relevant conditions. In particular, data showed that P. re-strictum MMS417 is able to produce lipids that include fatty acids usually produced by the mussel itself. This study also provides insight into the P. restrictum adaptation to marine salinity through fatty acids alteration. and shows that lipid metabolisms if far more altered in an OSMAC approach than the specialized metabolism. This study finally highlights the need for using environnement-mimicking culture conditions to reveal the metabolic potentialities of marine microbes.