Metabolomics studies of secondary metabolites from co culture of Fusarium sp. and Streptomyces sp. in the search for new potential antibiotics

The discovery of new secondary metabolites from endophytes becomes more challenging in natural products chemistry. Different approaches have been applied in order to increase the probability production of new metabolites from microbial. Bacteria and fungi interact within the host plant and stimulate competition for nutrients and spaces regarded as a major ecological factor that induce bioactive secondary metabolites. A lot of studies proved bacteria and fungi produce promising secondary metabolites for new antibiotic, anticancer and antioxidant agents. Thus, culturing two different microbes in the same media vessel rather than strains cultured independently, leads to direct interaction which may trigger the expression of “silent” biosynthetic pathway to produce novel secondary metabolites. In this study, we report the production of new secondary metabolites from co-cultures between Fusarium sp. isolated from mangrove plant Avicennia lanata and Streptomyces strain SUK10 obtained from Shorea ovalis. Prior to this study, metabolomics has been applied to identify and optimize the production of bioactive secondary metabolites in co cultures with different culture media at different growth stages. Metabolomic studies were afforded by both high resolution mass spectrometry and NMR spectroscopy. Metabolomic profiling data was processed by utilizing the quantitative expression analysis software Mzmine 2.10 coupled with macro analysis and supported with Antimarin database for dereplication studies. SIMCA P+ 13.0 was used to prove that the optimization models were statistically sound. Later, the co culture was scaled up either in liquid culture media (25 Litres) for 30 days. Crude extracts were fractionated using several high-throughput chromatographic techniques and subjected to bioactivity-guided isolation work for anti-trypanosomal and anti-microbial active metabolomes. Structure elucidation of isolated secondary metabolites was achieved using 2D-NMR and HRESI-MS.

Keywords: Metabolomics, co culture, Fusarium sp., Streptomyces sp.