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

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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.