Stress-driven Discovery of Natural Products from Extreme Marine Environment- Kueishantao Hydrothermal Vent, a Case Study of Metal Switch Valve

Marine hydrothermal vent microbial habitats are strongly influenced by elevated levels of heavy metals. Hydrothermal microorganisms respond rapidly to the changes in the concentrations and availability of metals within their environment, where geothermally heated water reacts with its host rock forming fluids that nourish a diverse array of geothermally dependent microorganisms. Most marine fungi possess a remarkable capability for the synthesis of a broad variety of biologically active secondary metabolites. One major obstacle in identifying secondary metabolites, however, is the known phenomenon of sleeping gene clusters and non-activated biosynthesis pathways which are present, but latent under standard screening conditions. Here, we proceed to show that non-activated or inert biosynthesis pathways can be awakened by the elicitation of heavy metal stress. In order to gain a more detailed insight into the nature of metal mediated products in marine fungi a chemical screening with extracts of biomass of two fungal strains derived from metal-rich Kueishantao hydrothermal vent environments was carried out to assay the influence of heavy metals on secondary metabolic patterns of marine fungi. Metabolite patterns of cultures grown in minimal media were compared to copper (or cadmium) spiked parallels. The results showed that contrarily to the widely held opinion of metals as hindrance in secondary metabolism, metals can induce synthesis of metabolites with a backbone not detected or detected as minor products in the normal cultures without metal stress. Hence, putative latent biosynthesis pathways in the hydrothermal vent fungi were deduced to be activated and switched by metals. Stress-driven discovery of natural products from hydrothermal vent fungi strain is a valid strategy to unveil the untapped reservoir of small molecules from hydrothermal vent environment.