Exploring plant and lichen-associated microbial diversity for discovery of small-molecule bioactive agents

Plant and lichen-associated microorganisms represent a largely untapped resource of small-molecule natural products with chemical structures that have conceivably been optimized by evolution for biological and/or ecological relevance. In our search for natural products with bioactivity and/or novel structures, we have investigated numerous fungal strains living in association with plants and lichens. Extracts and/or pure compounds derived from cultures of these fungal strains have been screened in assays relevant for anticancer, anti-HIV and anti-TB drug discovery, and plant stress tolerance. Organisms producing extracts found to be active in these assays were cultured on large-scale and the derived extracts have been subjected to bioactivity-guided fractionation to obtain a variety of natural products with bioactivity and/or novel structures suggesting the potential of this under-explored niche for small-molecule natural products with novel structural types and/or pharmaceutical and agricultural applications. Isolation, structure elucidation, bioactivity and possible biosynthetic origin of some selected small-molecule metabolites and the significance of their natural occurrence will be presented.

This work was supported by grants from NCI (USA), NIGMS (USA), CNPq (Brazil), and Arizona Biomedical Research Commission.