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通过提供以前从我们的2000多个蓝藻菌株的培养物中分离的结构多样的天然产物的集合来填补分子库小分子库（MLSMR）中的空白。三十年的天然产物研究揭示了一系列化合物，它们占据了目前MLSMR中没有的独特生物活性化学空间。这些化合物中只有少数存在可行的合成路线，我们的大多数培养菌株都是该系列所独有的。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，可以扩大MLSMR，与该RFA的高优先目标一致，即收购结构多样化的天然产品，这些产品可以在未来可靠地重新供应。鉴于天然产物作为生化探针和治疗先导物的历史重要性，将这些化合物纳入MLSMR的理由和潜在益处是明确的。 在这方面，该项目的具体目标是：1。在Patterson摩尔培养物保藏中心培养已知可产生MLSMR中未列出的天然产物的独特蓝藻菌株。至少有25种菌株被作为发酵的目标。2.从这些提取物中分离已知化合物和相关类似物并对其进行结构表征，以提供足够的数量提交给MLSMR。3.每年增加25-50个培养物中的分离株数量，并检查这些分离株是否具有独特的化学支架。 公共卫生相关性：培养的细菌是一种有价值的化学物质来源，可用于更好地了解细胞生物学，并有助于新药的开发。在过去的三十年里，夏威夷大学的科学家从这些来源中发现了独特的分子，这将是对MLSMR的宝贵补充。

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.