Marine natural products as antimicrobial chemical defenses and sources of potential drugs.

Marine organisms including macroalgae, sponges, and other invertebrates, and microbes are widely recognized sources of an impressive array of structurally unusual compounds. Herein, I evaluate the hypothesis that macroalgal natural products play a role in defending these organisms against potentially pathogenic microbes in the marine environment. Further, I combine these ecology-driven investigations with evaluation of algal natural products as sources of novel human drugs. This combined approach resulted in discovery of 15 novel natural products from two tropical red algae, Callophycus serratus and an unidentified crustose red alga. These new molecules included seven novel carbon-carbon connectivity patterns, not previously reported in the synthetic or natural product literature, illustrating the abundance of secondary metabolite diversity among marine macroalgae. Further, many compounds exhibited both biomedical and ecological activities, suggesting the synergistic potential of combined biomedical/ecological investigations in providing drug leads as well as insights into the natural functions of secondary metabolites. Bromophycolides and callophycoic acids, natural products from C. serratus, inhibited growth of the marine fungal pathogen Lindra thalassiae. Spatially-resolved desorption ionization mass spectrometry (DESI-MS) revealed that these antifungal natural products were found at specific sites on algal surfaces. Finally, assessment of antimicrobial chemical defenses among extracts from 72 collections of tropical red algae revealed that nearly all algae were defended against at least one marine pathogen or saprophyte and further suggested the untapped potential of ecological investigations in the discovery of novel chemistry. Future investigations of chemically-mediated interactions between hosts and microbes will continue to increase understanding of these highly complex biological interactions and may provide valuable insights for drug discovery.