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Eric W. Schmidt

Assistant Professor of Medicinal Chemistry

B.S. University of California, San Diego

Ph.D. University of California, San Diego

Research

References

ews1@utah.edu

Eric Schmidt's Lab Page

Research

The world's ocean and terrestrial habitats harbor an enormous wealth of biodiversity, which serves as the source for numerous small molecule pharmaceuticals, molecular probes, and drug leads. More than 50% of all currently prescribed drugs originate in bacteria, fungi, plants, and marine invertebrates, but by far the majority of natural pharmaceuticals remain to be discovered. In the genomic era, it is now possible to rapidly sequence and manipulate genes to synthesize and discover drugs by genetic engineering. We are combining elements of biodiversity, genetic engineering, and genome sequencing in the discovery of drugs and drug biosynthetic pathways.

Marine Invertebrates. Filter-feeding animals in the oceans have been rich sources of new natural products, but supply of these promising compounds for clinical development is expensive and not environmentally benign. Many of these animals are laced with symbiotic bacteria that are often thought to be the true source of these compounds. We are working on basic scientific questions about how molecules are made by marine invertebrates and their bacterial symbionts, using tools such as genome sequencing and homology-based cloning. Once pathways are identified, biochemical approaches are used to better understand how molecules are made and how they can be manipulated by genetic engineering. Beyond pathway discovery and biochemistry, we are interested in how natural product pathways help to maintain symbioses and how these pathways evolve. Information from these studies can be used to design new drugs, supply promising marine natural products for clinical development, and provide a better understanding of biodiversity on coral reefs and other marine habitats. In particular, we are studying the biosynthesis of cyclic peptides in the cyanobacterial symbiont, Prochloron didemni , and are involved in a genome sequencing project for this organism. We are also working on biosynthesis of compounds produced by marine sponges and their symbionts.

Filamentous Fungi. These eukaryotes often produce natural products with unusual structures and potent bioactivities, but the genetics and biochemistry of natural product synthesis is much less developed in fungi than in bacteria. In addition, less than 5% of filamentous fungi have been cultured, and the untapped pool of biosynthetic diversity is likely to be enormous. We recently discovered a novel hybrid polyketide synthase-peptide synthetase hybrid enzyme that is responsible for production of a tetramic acid, equisetin, in the fungus Fusarium heterosporum . Studies are underway to determine the biochemical mechanisms of equisetin production. We are using this pathway as a platform for further drug discovery and synthesis via genetic engineering. We are particularly interested in accessing the uncultured fungal diversity. For example, numerous fungal species inhabit each insect, plant, and animal, yet very few have been cultured. Some biosynthetic pathways may be only expressed in symbiotic environments; since they are likely to be unnecessary for survival on rich medium, they will not be discovered in typical natural products isolation protocols. Genetic tools allow us to access this diversity.

References