Time-Dependent Production of the Bioactive Peptides Endolides A and B and the Polyketide Mariline A from the Sponge-Derived Fungus Stachylidium bicolor 293K04

Previous investigations of the sponge-derived fungus Stachylidium bicolor (S. bicolor) 293K04 led to the isolation of the biosynthetically unusual polyketides marilines A-C and the bioactive tetrapeptides endolides A-B, identified as potential neuropathic drug leads. Furthermore, prior extended solid cultivation of S. bicolor 293K04 for 60 days resulted in a significant increase of polyketide yield, and the isolation of seven new polyketides. Due to the interest in endolide activity, unusual biosynthetic diversity, and the late stage polyketide production, we studied the cultivation conditions for determining the production time distribution and yields of these secondary metabolites. Results indicated a first production phase of secondary metabolite dominated by peptides, after 21-23 days. Polyketide mariline A1/A2 only started at day 35 of growth, an unusually late period for secondary metabolite expression. This unusual bimodal sequential expression of different families of secondary metabolites suggests value in exploring extended cultivation times to identify novel bioactive fungal compounds.