Using the Marine Natural Product Psymberin as a Discovery Template for Biosynthetic Engineering and Biosynthetic Product Investigation

使用海洋天然产物 Psymberin 作为生物合成工程和生物合成产品研究的发现模板

• 批准号: 0617056
• 负责人: Phillip Crews
• 金额: --
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-10-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0617056&HistoricalAwards=false
• 关键词: Using; Marine; Natural; Product; Psymberin

The goal of this application is to launch a cooperative research program in bioorganic chemistry between U.S. and German academic scientists. The Marine Natural Products group at the University of California Santa Cruz, Department of Chemistry and Biochemistry, in the USA led by Professor Phil Crews will work side-by-side with the Marine Biosynthetic Engineering group at the Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, in Germany led by Associate Professor Joern Piel. In 2004, the Crews lab reported the structure of psymberin isolated from Psammocinia sp. sponges collected in Papua New Guinea. The marine natural product psymberin appears to be erratically produced and is related to the terrestrial-derived pederin family of compounds. In 2005, the Piel group constructed metagenomic libraries of Paederus fuscipes beetles and the sponge Theonella swinhoei and was able to isolate the genes required for the biosynthesis of pederin and the related onnamides. The intent of this proposed research is to extend this technology to a pharmacologically highly promising marine system. The psymberin-producing sponge including possible microbial symbionts will be the basis for the six program goals that are: (1) to fully define the structural diversity of the psymberin class of PKS-NRPS products by exploring chemotypes and morphotypes of Psammocinia sp.; (2) to correlate the appearance of psymberin in sponges with its microbial populations; (3) to engage in the isolation, sequencing, and expression of psymberin genes; (4) to use the results of aims #2 and #3 to search for psymberin producing microbial strains; (5) to expose USA and German students to the advantages and process of collaborative research; and (6) to provide USA and German students perspectives on ethics in science.With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are supporting the work of Professor Phillip O. Crews, of the Department of Chemistry and Biochemistry at the University of California at Santa Cruz. Professor Crews and his collaborator, Joern Piel, of the Kekule Institute of Organic Chemistry and Biochemistry at the University of Bonn, are exploring the means by which marine sponges synthesize an unusual group of molecules intriguingly related structurally to a class of molecules produced by terrestrial organisms. This study will address unanswered questions of marine bioorganic chemistry, leading to an understanding of how marine organisms produce such complex molecules, which not infrequently lead the way to the discovery of new pharmaceutical agents. A broad skill set is required and this can only be done through a collaborative approach. The success of this program will serve as a model for international scholarly collaborative research and will demonstrate that a multinational collaboration in marine chemical biology can be successful.

该应用程序的目标是启动美国和德国学术科学家之间的生物有机化学合作研究项目。由 Phil Crews 教授领导的美国加州大学圣克鲁斯分校化学与生物化学系海洋天然产品小组将与由 Joern Piel 副教授领导的德国波恩大学凯库勒有机化学与生物化学研究所的海洋生物合成工程小组并肩工作。 2004年，Crews实验室报告了从Psammocinia sp.中分离出的psymberin的结构。巴布亚新几内亚采集的海绵。海洋天然产物薄荷素的产生似乎不稳定，并且与陆地来源的佩德林化合物家族有关。 2005年，Piel小组构建了Paederus fuscipes甲虫和海绵Theonella swinhoei的宏基因组文库，并能够分离出pederin和相关onnamides生物合成所需的基因。这项研究的目的是将这项技术扩展到药理学上非常有前途的海洋系统。包括可能的微生物共生体在内的产生 psymberin 的海绵将成为六个计划目标的基础，这些目标是：（1）通过探索 Psammocinia sp. 的化学型和形态型来全面定义 PKS-NRPS 产品的 psymberin 类的结构多样性； (2) 将海绵中的精神琥珀素的出现与其微生物种群相关联； （3）从事psymberin基因的分离、测序及表达； (4)利用目标#2和#3的结果来寻找产生薄荷素的微生物菌株； (5) 让美国和德国学生了解合作研究的优势和过程； (6) 为美国和德国学生提供有关科学伦理的观点。有机与高分子化学项目和国际科学与工程办公室通过该奖项支持加州大学圣克鲁斯分校化学与生物化学系 Phillip O. Crews 教授的工作。克鲁斯教授和他的合作者波恩大学凯库勒有机化学和生物化学研究所的乔恩·皮尔正在探索海洋海绵合成一组不寻常分子的方法，这些分子在结构上与陆地生物产生的一类分子有趣地相关。这项研究将解决海洋生物有机化学中尚未解答的问题，从而了解海洋生物如何产生如此复杂的分子，这通常会导致新药剂的发现。需要广泛的技能，而这只能通过协作方法来完成。该计划的成功将成为国际学术合作研究的典范，并将证明海洋化学生物学领域的跨国合作可以取得成功。