DFG-NSF-Antrag: Using the marine natural product psymberin as a discovery template for biosynthetic engineering and biosynthetic product investigation

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There is overwhelming evidence that many bioactive natural products isolated from marine invertebrates are synthesized by as-yet unculturable bacterial symbionts. However, the elusive lifestyle of these microbes has so far precluded the systematic exploration of their pharmacological potential. With a set of newly developed metagenomic techniques, this collaborative project aims to contribute to a better understanding of natural product symbiosis. We will study the chemical ecology, evolution and genetics of the producer of psymberin, a highly promising anticancer agent with selective activity against solid tumor cells. Psymberin, isolated from a Psammocinia sp. sponge, is a member of the pederin family of polyketides found in beetles and sponges. Our contribution to this collaboration is the isolation of genomic regions carrying the psymberin biosynthesis genes from the sponge metagenome, guided by sequence data from previous studies on the symbiotic pederin and onnamide producers. The genes will then be analyzed to deduce evolutionary and taxonomic information and finally heterologously expressed in a culturable host to generate a sustainable psymberin source.