Accessing Cyanobacterial Chemical Diversity: A Unique Natural Product Library

描述(申请人提供)：这项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集合中分离出来的结构多样化的天然产物来填补分子库小分子储存库(MLSMR)的空白。三十年来对这一系列天然产品的研究揭示了一系列化合物，它们占据了目前MLSMR中没有的独特的生物活性化学空间。可行的合成路线只存在于这些化合物中的一小部分，并且我们的大多数培养菌株是这个集合所独有的。因此，这些代谢物不能从任何其他来源获得。因此，这项提议代表着一个真正独特的机会，可以扩大MLSMR，符合本区域管理局的一个高度优先目标，即获得结构多样化的天然产品，这些产品将来可以可靠地重新供应。考虑到天然产品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的理由和潜在好处是显而易见的。 在这种背景下，该项目的具体目标是：1.培养Patterson Moore培养库中独特的蓝藻菌株，这些菌株可生产MLSMR中没有的天然产品。至少有25株菌株已被确定为发酵目标。2.从这些提取物中分离已知的化合物和相关类似物并对其结构进行表征，以便提供足够的数量提交MLSMR。3.每年增加25-50个培养物分离株的数量，并检查这些分离株以寻找独特的化学支架。 与公共卫生相关：培养的细菌是一种经证实的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。夏威夷大学的科学家在过去的三十年里从这些来源中识别出的独特分子将是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.