Marine biotechnology

Stevensine is a biologically active secondary metabolite produced by several marine sponges, including Teichaxinella morchella. Two in vitro methods were used to investigate the biosynthetic origin of stevensine in the sponge T. morchella. A cell-free enzyme extract was developed to test for the incorporation of the potential radiolabeled metabolic precursors histidine, arginine, ornithine, and proline. Secondly, cell cultures of T. morchella were used to determine the biosynthetic origin of stevensine from the radiolabeled amino acids histidine, arginine, ornithine, and proline. Histidine and ornithine/proline were converted to stevensine in the cell culture system. This represents the first study involving the use of cell cultures of a marine invertebrate to investigate the biosynthesis of a biologically active natural product. An understanding of the biosynthetic process leading to the production of this compound in the source organism could lead to the development of more efficient and environmentally safer production methods.

The projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the Family Petrosiidae. Although initially purified following activity in a (Sb(B-catenin/Tcf4 assay they were later followed using tumor cell line cytotoxicity assays. Petrosiquinone A was the more active of the two compounds with moderate cytotoxicity in the DLD-1, PANC-1, and AsPC-1 cell lines. In Chapter 3, the isolation and structure elucidation of two new marine-derived macrolides, madeirolide A and B, isolated from a deep-water lithistid sponge of the genus Leiodermatium is described.