Abstract:[Background] Fungi produce diverse secondary metabolites to adapt to their habitats. [Objective] To compare the secondary metabolites of Eurotium cristatum strains from two habitats (Fuzhuan brick tea and ocean) in PDA and explore the regulatory effect and mechanism of the tea leaf medium on the metabolites of ocean originated E. cristatum. [Methods] Liquid chromatography-mass spectrometry combined with feature-based molecular networking was employed to analyze the differences of secondary metabolites of the two strains of E. cristatum, and the changes in non-volatile metabolites of the ocean originated strain in the tea leaf medium were analyzed by the multivariate statistical method. In addition, we investigated the effects of indirect and direct carbon sources on the secondary metabolites of the ocean originated strain. [Results] Firstly, the two strains of E. cristatum presented similar polyketone synthesis capacity but significant differences in non-ribosomal peptide synthesis. Specifically, the tea-derived strain produced isopentenyl cyclic dipeptide, while the ocean originated strain produced oligopeptides. Secondly, the domestication in the tea leaf medium for 5 days induced changes in the secondary metabolic pathways of the ocean originated strain. Finally, some metabolites of the ocean originated strain in the tea leaf medium were identical to those in the medium with indirect carbon source. [Conclusion] There were significant differences in the secondary metabolic pathways between E. cristatum strains from the two habitats. The short-term domestication in the tea leaf medium changes the secondary metabolic pathways of the ocean originated strain, which may be partly due to the lifting of carbon catabolite repression.