OSMAC Investigation Directed by Genome Information Led to the Discovery of Additional Five Types of Secondary Metabolites From Deep-Sea Derived Penicillium Sp. SCSIO sof101.

Marine fungi are considered important resources for new lead compounds in One Strain Many Compounds (OSMAC) strategy. In particular, deep-sea derived fungi have been deemed potent for novel bioactive structures due to their extreme living environment and evolution of special biosynthetic gene clusters (BGCs) for secondary metabolites. Chemical investigations of the deep-sea derived Penicillium sp. SCSIO sof101 led to the discovery of 5 types of 21 bioactive compounds, including the significant anti-Gram-negative bacterial compound sulfoxanthicillin. Bioinformatics analysis of the strain revealed 56 BGCs for the secondary metabolites. This information guided the further culture optimization, which led to the discovery of another five types of secondary metabolites (1-11), including one non-ribosomal peptide and polyketide (NRP-PK) type compounds (1-3), which included a new compound (1), one NRP type compounds (4-5), and three PK types compounds (6-11). The structure of compound 1 was elucidated by spectral analyses including HR-ESI-MS, 1D and 2D NMR, and chemical derivatization approaches. Compound 1 was inactive in the evaluation of antibacterial activity and cytotoxicity. Its biosynthetic pathway was proposed. This finding paves the way for further mining of OSMAC potent from the deep-sea derived strain.