The long-term objective of this research is to fill a void in the Molecular Libraries Small Molecule Repository (MLSMR) by providing a collection of structurally diverse natural products previously isolated from our culture collection of over 2000 cyanobacterial strains. Thirty years of natural product research on this collection has revealed an array of compounds that occupy a unique biologically active chemical space not currently represented in the MLSMR. Viable synthetic routes exist to only a few of these compounds and most of our culture strains are unique to this collection. As such, these metabolites are not available from any other sources. Thus, this proposal represents a truly unique opportunity to expand the MLSMR consistent with a high priority goal of this RFA, the acquisition of structurally diverse natural products that can be reliably re-supplied in the future. The rationale for and potential benefit of the inclusion of these compounds in the MLSMR is clear given the historic importance of natural products as biochemical probes and therapeutic leads. In that vein, the specific goals of this project are: 1. To culture the unique cyanobacterial strains in the Patterson Moore Culture Collection known to produce natural products not represented in the MLSMR. At least 25 strains have been targeted for fermentation. 2. To isolate and structurally characterize known compounds and related analogues from these extracts in order to provide sufficient quantities for submission to the MLSMR. 3. To expand the number of isolates in the culture collection by 25-50 per year and examine these for unique chemical scaffolds.
Cultured bacteria are a valuable proven source of chemicals that can be used to better understand cell biology and can aid in the development of new drugs. The unique molecules identified by scientists at the University of Hawaii over the last thirty years from these sources would be a valuable addition to the MLSMR.