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

该申请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计划。由Phil Crews教授领导的美国加州大学圣克鲁斯分校化学和生物化学系的海洋天然产物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并肩工作，由Joern Piel副教授领导。2004年，克鲁斯实验室报道了从巴布亚新几内亚采集的Psammocinia sp.海绵中分离出的Psymberin的结构。海洋天然产物psymberin似乎是不规则地产生，并与陆地衍生的pederin家族化合物有关。在2005年，Piel小组构建了黑翅长角甲虫和海绵Theonella swinhoei的宏基因组文库，并能够分离出生物合成pederin和相关onnamides所需的基因。这项研究的目的是将这项技术扩展到一个非常有前途的海洋系统。包括可能的微生物共生体的产生Psymberin的海绵将是六个计划目标的基础，即：（1）通过探索Psammocinia sp.的化学型和形态型，充分确定PKS-NRPS产物的Psymberin类的结构多样性; (2)将海绵中Psymberin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）使用目标#2和#3的结果来寻找产生Psymberin的微生物菌株;（5）向美国和德国学生展示合作研究的优势和过程;及（6）为美国及德国学生提供有关科学道德的观点。有了这个奖项，有机及高分子化学计划及国际科学及工程处支持菲利普教授的工作。位于圣克鲁斯的加州大学化学和生物化学系的克鲁斯说。Crews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Joern Piel正在探索海绵合成一组不寻常的分子的方法，这些分子在结构上与陆地生物产生的一类分子有着有趣的关系。这项研究将解决海洋生物有机化学的悬而未决的问题，从而了解海洋生物如何产生这种复杂的分子，这并不罕见地导致发现新的药剂。需要广泛的技能，这只能通过合作的方式来完成。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.