Defense metabolites from the marine sponge Verongia aerophoba

The marine sponge Verongia aerophoba (syn. Aplysina aerophoba) accumulates isofistularin-3 and aerophobin-2 as major brominated isoxazoline alkaloids. Following disrupture of the compartmentation (e.g. by wounding) both isofistularin-3 and aerophobin-2 are enzymatically converted into aeroplysinin-1 which in turn gives rise to a dienone. Aeroplysinin-1 and dienone were shown to exhibit pronounced biological activities in various bioassays with marine organisms (bacteria, algae and molluscs) whereas their biogenetic precursors isofistularin-3 and aerophobin-2 were either inactive or exhibited only marginal activity. In the agar plate diffusion assay, aeroplysinin-1 and dienone were antibiotically active against eight different Gram-positive or Gram-negative marine bacteria including Alteromonas, Moraxella and Vibrio spp. Towards the marine Photobacterium phosphoreum the EC(50)s Of aeroplysinin-1 and dienone were 3.45 and 1.37 mu M, respectively. Both compounds inhibited also the growth of the marine microalgae Coscinodiscus wailesii and Prorocentrum minimum. Towards the former, the EC(50)s of aeroplysinin-1 and dienone were 5.6 and 27.9 mu M, respectively. In addition to their growth inhibitory activity, aeroplysinin-1 and dienone were algicidal as evident by their damaging effects on the algal cellular membranes. The polyphagous marine gastropod Littorina littorea was repelled when exposed to either aeroplysinin-1 or dienone that were added to seawater. The EC(50) of the most active compound aeroplysinin-1 was observed at 0.1 mM. It is suggested that the enzymatically catalysed conversion of brominated metabolites in V. aerophoba represents a wound-induced defense mechanism hitherto unreported from the marine environment.