Accessing Cyanobacterial Chemical Diversity: A Unique Natural Product Library

描述（由申请人提供）：本研究的长期目标是填补分子文库小分子库（MLSMR）的空白，提供先前从我们的2000多种蓝藻菌株培养收集中分离出的结构多样的天然产物。经过30年的天然产物研究，发现了一系列化合物，它们占据了MLSMR中目前没有的独特的生物活性化学空间。这些化合物中只有少数存在可行的合成路线，而我们的大多数培养菌株都是这个集合所独有的。因此，这些代谢物无法从任何其他来源获得。因此，该提案代表了一个真正独特的机会，以扩大MLSMR与该RFA的高优先级目标一致，即获得结构多样化的天然产品，可以在未来可靠地重新供应。考虑到天然产物作为生化探针和治疗线索的历史重要性，将这些化合物纳入MLSMR的基本原理和潜在益处是明确的。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.