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

该应用程序的目标是启动美国和德国学术科学家在生物有机化学方面的合作研究计划。由菲尔·克鲁斯教授领导的美国加州大学圣克鲁斯大学化学和生物化学系海洋天然产品小组将与德国波恩大学凯库勒有机化学和生物化学研究所的海洋生物合成工程小组由Joern Piel副教授领导。2004年，Crews实验室报道了从Psammocinia sp.中分离出的psymberin的结构。在巴布亚新几内亚收集的海绵。海洋天然产物psymberin似乎是不稳定地产生的，与陆源Pederin家族化合物有关。2005年，Piel团队构建了金龟子隐翅虫和海绵Theonella swinhoei的元基因组文库，并能够分离出Pederin生物合成所需的基因和相关的鱼腥草素。这项拟议研究的目的是将这项技术扩展到药理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psymberin产生海绵将成为六个计划目标的基础，这六个目标是：(1)通过探索Psammocinia sp.的化学类型和形态类型，充分定义psymberin类PKS-NRPS产品的结构多样性；(2)将psymberin在海绵中的出现与其微生物种群相关联；(3)从事psymberin基因的分离、测序和表达；(4)利用AIMS#2和#3的结果搜索psymberin产生微生物菌株；(5)向美国和德国学生展示合作研究的优势和过程；以及(6)为美国和德国学生提供关于科学伦理的观点。通过这一奖项，有机和高分子化学项目和国际科学与工程办公室正在支持加州大学圣克鲁斯分校化学和生物化学系菲利普·O·克鲁斯教授的工作。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约恩·皮尔正在探索海洋海绵合成一组不同寻常的分子的方法，这些分子在结构上与陆地生物产生的一类分子有有趣的联系。这项研究将解决海洋生物有机化学中悬而未决的问题，从而了解海洋生物如何产生这种复杂的分子，这往往会导致新的药剂的发现。需要广泛的技能，而这只能通过协作的方法来实现。该项目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。

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.