Eric W. Schmidt

Eric W. SchmidtWilliam R. Droschkey Endowed Chair in Pharmacy, Professor of Medicinal Chemistry L. S. Skaggs Pharmacy Institute, Adjunct Professor of Biology, College of Science

Office:

Phone: 801.585.5234
Fax: 801.585.6208

Education:

NIH Fellowship 1999-2001 Johns Hopkins University
Ph.D. 1999 Scripps Institution of Oceanography
B.S. 1994 University of California at San Diego


Research Interests

Natural Products: Biodiversity, Drug Discovery, Synthetic Biology

snailstuff

Marine Natural Products and Symbiosis: The Tunicates

The tunicates shown above are animals collected from a single site in the tropical Pacific Ocean (photo by Chris Ireland). They are an excellent source of novel natural products, including clinically applied anticancer drugs. Strikingly, most of the interesting natural products in tunicates are produced by symbiotic bacteria, and not by the animals themselves. Using the tools of organic chemistry, metagenomics, synthetic biology, and biochemistry, we strive to understand the origin, biosynthesis, and roles of these natural products. Further, we apply this understanding to the discovery of novel pharmaceuticals and the development of new synthetic biology tools that will impact human health and biotechnology.

Natural Products from Other Sources

Although our lab has focused on marine natural products and symbiosis, we also aim to discover and understand natural products from a variety of other sources, such as terrestrial bacteria and fungi. The common theme to these projects is that they involve either unexplored and unstudied habitats, or novel biosynthetic machinery that is not well understood. Thus, these projects provide us with the opportunity to explore the basic science of natural chemicals from biologically diverse sources.

Drug Design and Discovery

We work with many different biologists, pharmacologists, and others to find compounds that target important human diseases. A major focus has been in neuroscience, where discover ligands that act on dorsal root ganglion neurons, via "constellation pharmacology." We have also reported novel agents that target infectious agents and cancers.

Synthetic Biology

We have been interested in biosynthetic pathways that are inherently engineerable, with a focus on the ribosomally synthesized and posttranslationally modified peptides (RiPPs). By understanding the substrate requirements, we are generating a set of interchangeable biosynthetic tools that can be used to decorate peptides in defined ways and to synthesize large libraries of derivatives for drug screening.


Related Links

Schmidt's Laboratory Website

Visit Schmidt's Laboratory website


Publications

2014

77. Jadulco, R.C.; Koch, M.; Kakule, T.B.; Orendt, A.; He, H.; Janso, J.; Carter, G.; Schmidt, E.W.; Barrows, L.R. Pyrrolocins A-C: cis- and trans-Decalin tetramic acid analogues from an endophytic fungus. J. Nat. Prod. 2014. epub.

76. Kakule, T.; Lin, Z.; Koch, R.; Koch, M.; Barrows, L.R.; Schmidt, E.W. Native promoter strategy for high-yielding synthesis and engineering of fungal secondary metabolites. ACS Synth. Biol. 2014. epub.

75. Lin, Z.; Koch, M.; Aziz, M.H.A.; Tianero, M.D.; Galindo-Murillo, R.; Cheatham, T.E.; Barrows, L.R.; Reilly, C.A.; Schmidt, E.W. Oxazinin A, a pseudodimeric natural product of mixed biosynthetic origin from a filamentous fungus. Org. Lett. 2014. Epub.

74. Jacinto, M.P.V.; Flores, M.S.; Lin, Z.; Concepcion, G.P.; Schmidt, E.W.; Faulkner, S.; Villaraza, A.J.L. Synthesis and bioactivity of nobilamide B. RSC Advances 2014 epub

73. Ruffner, D.E.; Schmidt, E.W.; Heemstra, J.R. Assessing the combinatorial potential of the RiPP cyanobactin tru pathway. ACS Synth. Biol. 2014 epub.

72. Teichert, R.W.; Schmidt, E.W.; Olivera, B.M. Constellation Pharmacology: A new paradigm for drug discovery. Ann. Rev. Pharm. Tox. 2014 in press.

71. Schmidt, E.W. The secret to a successful relationship: Lasting chemistry between ascidians and their symbiotic bacteria. Invert. Biol. 2014 epub.

70. Tianero, M.D.; Kwan, J.C.; Wyche, T.; Koch, M.; Barrows, L.R.; Bugni, T.S.; Schmidt, E.W. Species specificity of symbiosis and secondary metabolism in ascidians. ISME J. 2014 epub.

69. Lin, Z.; Zachariah, M.M.; Marett, L.; Hughen, R.W.; Teichert, R.W.; Concepction, G.P.; Haygood, M.G.; Olivera, B.M.; Light, A.R.; Schmidt, E.W. Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis. J. Nat. Prod. 2014. epub.

68. Sardar, D.; Pierce, E.; McIntosh, J.A.; Schmidt, E.W. Recognition sequences and substrate evolution in cyanobactin biosynthesis. ACS Synth. Biol. 2014 epub.

67. Kwan, J.C.; Tianero, M.D.; Donia, M.S.;Wyche, T.P.; Bugni, T.S.; Schmidt, E.W. Host control of symbiont natural product chemistry in cryptic populations of the tunicate Lissoclinum patella. PLoS ONE2014,9, e95890

66. Schmidt, E.W. Biosynthetic approaches to marine drug discovery and development. In: Marine Drugs, Baker, B editor. 2014 invited chapter.

65. Lin, Z.; Koch, M.; Pond, C.D.; Mabeza, G.; Seronay, R.A.; Concepcion, G.P.; Barrows, L.R.; Olivera, B.M.; Schmidt, E.W. Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp. J. Antibiot.2014,67,121-126.

2013

64. Kwan, J.C.; Schmidt, E.W. Bacterial endosymbiosis in a chordate host: Long-term co-evolution and conservation of secondary metabolism. PLoS ONE 2013 in press.

63. Lin, Z.; Marett, L.; Hughen, R.W.; Flores, M.; Forteza, M.; Ammon, M.A.; Concepcion, G.P.; Espino, S.; Olivera, B.M.; Rosenberg, G.; Haygood, M.G.; Light, A.R.; Schmidt, E.W. Neuroactive diol and acyloin metabolites from cone snail-associated bacteria. Bioorg. Med. Chem. Lett. 2013, 23, 4867-4869. Link

62. Kakule, T.; Sardar, D.; Lin, Z.; Schmidt, E.W. Two related pyrrolidinedione synthetase loci in Fusarium heterosporum ATCC 74349 produce divergent metabolites. ACS Chem. Biol. 2013 epub. Link

61. Adnani, N.; Ellis, G. A.; Kwan, J. C.; Wyche, T. P.; Schmidt, E. W.; Bugni, T. S. in Natural Product Analysis: Instrumentation, Methods, and Applications.  Havlicek, V. and Spizek, J. Eds.  John Wiley & Sons, Inc.: Hoboken, NJ. 2013; In Press.

60. McIntosh, J.A.; Lin, Z.; Tianero, M.D.; Schmidt, E.W. Aestuaramides, a Natural Library of Cyanobactin Cyclic Peptides Resulting from Isoprene-Derived Claisen Rearrangements. ACS Chem. Biol. 2013, epub. Link

59. Elshahawi, S.I.; Trinidade-Silva, A.E.; Hanora, A.; Han, A.W.; Flores, M.; Vizzoni, V.; Schrago, C.G.; Concepcion, G.P.; Distel, D.L.; Soares, C.A.; Schmidt, E.W.; Haygood, M.G. A boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills. Proc. Natl. Acad. Sci. U S A  2013, E295-304. Link

58. Lin, Z.; Torres, J.; Ammon, M.A.; Marett, L.; Teichert, R.W.; Reilly, C.A.; Kwan, J.C.; Hughen, R.W.; Flores, M.; Peraud, O.; Light, A.; Villaraza, A.; Haygood, M.G.; Concepcion, G.P.; Olivera, B.M.; Schmidt, E.W. A bacterial source for mollusk pyrone polyketides. Chem. Biol2013, 20, 73-81. Link

57. Arnison, P.G.; Bibb, M.J.; Bierbaum, G.; Bowers, A.A.; Bugni, T.S.; Bulaj, G.; Camerero, J.A.; Campopiano, D.J.; Challis, G.L.; Clardy, J.; Cotter, P.D.; Craik, D.J.; Dawson, M.; Dittmann, E.; Donadio, S.; Dorrestein, P.C.; Entian, K.D.; Fischbach, M.A.; Garaveli, J.S.; Goransson, U.; Gruber, C.W.; Haft, D.H.; Hemscheidt, T.K.; Hertweck, C.; Hill, C.; Jaspars, M.; Kelly, W.L.; Klinman, J.P.; Kuipers, O.P.; Link, A.J.; Liu, W.; Marahiel, M.A.; Mitchell, D.A.; Moll, G.N.; Moore, B.S.; Muller, R.; Nair, S.K.; Nes, I.F.; Norris, G.E.; Olivera, B.M.; Onaka, H.; Patchett, M.L.; Piel, J.; Reaney, M.J.T.; Rebuffat, S.; Ross, R.P.; Sahl, H.-G.; Schmidt, E.W.; Selsted, M.E.; Severinov, K.; Shen, B.; Sivonen, K.; Tagg, J.R.; Tang, G.-L.; Sussmuth, R.E.; Tagg, J.R.; Tang, G.L.; Truman, A.W.; Vederas, J.C.; Walsh, C.T.; Walton, J.D.; Wenzel, S.C.; Willey, J.M.; van der Donk, W.A. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for nomenclature. Nat. Prod. Rep. 2013. epub. Link

2012

56. Schmidt, E.W. Decoding and recoding the ribosomal peptide universe. Chem. Biol. 2012 epub Link

55. Kwan, J.C.; Donia, M.S.; Han, A.; Hirose, E.; Haygood, M.G.; Schmidt, E.W. Genome streamlining for chemical defense in a coral reef symbiosis. Proc. Natl. Acad. Sci. U S A 2012, 109, 20655-20660. Link

54. Hou, Y.; Tianero, D.; Kwan, J.C.; Wyche, T.P.; Cole, M.R.; Ellis, G.A.; Vazquez-Rivera, E.; Braun, D.R.; Rose, W.E.; Schmidt, E.W.; Bugni, T.S. Structure and biosynthesis of the antibiotic bottromycin D. Org. Lett. 2012, 14, 5050-5053. Link

53. Agarwal, V.; Pierce, E.; McIntosh, J.; Schmidt, E.W.; Nair, S.K. Structures of cyanobactin maturation enzymes define a new family of transamidating proteases. Chem. Biol. 2012. epub. Link

52. Lin, Z.; Falkinham, J.O.; Tawfik, K.; Jeffs, P.; Cox, J.E.; Schmidt, E.W. Burkholdines from Burkholderia ambifaria: Antifungal agents and possible virulence factors. J. Nat. Prod. 2012, 75, 1518-1523. Link

51. Lin, Z.; Flores, M.; Forteza, I.; Concepcion, G.P.; Rosenberg, G.; Haygood, M.G.; Olivera, B.M.; Light, A.; Schmidt, E.W. Totopotensamides, polyketide-cyclic peptide hybrids from a mollusk-associated bacterium Streptomyces sp. J. Nat. Prod. 2012, 75, 644-649. Link

50. Kwan, J.C.; Schmidt, E.W. Cleaning up polyketide synthases. Chem. Biol. 2012 epub. Link

49. Schmidt, E.W.; Donia, M.S.; McIntosh, J.A.; Fricke, W.F.; Ravel, J. Origin and variation of ascidian metabolites. 2012. J. Nat. Prod. epub. Link

48. Tianero, D.; Donia, M.S.; Young, T.S.; Schultz, P.G.; Schmidt, E.W. Ribosomal route to small molecule diversity. J. Am. Chem. Soc. 2012, 134, 418-425. Link

2011

47. Donia, M.S.; Fricke, W.F.; Partensky, F.; Cox, J.; Elshahawi, S.I.; White, J.R.; Phillipy, A.M.; Schatz, M.C.; Piel, J.; Haygood, M.G.; Ravel, J.; Schmidt, E.W. Complex microbiome underlying secondary and primary metabolism in the tunicate-Prochloron symbiosis. Proc. Natl. Acad. Sci. U S A 2011, 108, E1423-E1432. Link

46. McIntosh, J.A.; Donia, M.S.; Nair, S.K.; Schmidt, E.W. Enzymatic basis of ribosomal peptide prenylation in cyanobacteria. J. Am. Chem. Soc. 2011, 133, 13698-13705. Link

45. Lin, Z.; Reilly, C.; Antemano, R.; Hughen, R; Marett, L.; Olivera, B.M.; Haygood, M.G.; Concepcion, G.P; Light, A.; Schmidt E.W. Nobilamides A-H, Long-Acting TRPV1 antagonists from mollusk-associated bacteria. J. Med. Chem. 2011, 54, 3746-3755. Link

44. Donia, M.S.; Ruffner, D.E.; Cao, S.; Schmidt, E.W. Accessing the hidden majority of marine natural products through metagenomics. ChemBioChem. 2011, 12, 1230-1236. Link

43. Donia, M.S.; Fricke, F.; Ravel, J.; Schmidt, E.W. Variation in tropical reef symbiont metagenomes defined by secondary metabolism. PLoS One  2011 6, (3), e17897. Link

42. Donia, M.S.; Schmidt, E.W. Linking chemistry and genetics in the growing cyanobactin natural products family. Chem. Biol. 2011, 18, 508-519. Link

41. Schmidt, E.W. Highlight: An enzymatic route to sunscreens. ChemBioChem 2011, 12, 363-365. Link

2010

40. Lin, Z.; Antemano, R.; Hughen, R.W.; Tianero, D.B.; Peraud, O.; Haygood, M.G.; Concepcion, G.P.; Olivera, B.M.; Light, A.; Schmidt, E.W. Pulicatins A-E, neuroactive thiazoline metabolites from cone snail-associated bacteria. J. Nat. Prod. 2010, 73, 1922-1926. Link

39. Schmidt, E.W.; Donia, M.S. Life in cellulose houses: symbiotic bacterial biosynthesis of ascidian drugs and drug leads. Curr. Op. Biotechnol. 2010, 21, 827-833. Link

38. McIntosh, J.A.; Robertson, C.R.; Agarwal, V.; Nair, S.; Bulaj, G.W.; Schmidt, E.W. Circular logic: Nonribosomal peptide-like macrocyclization with a ribosomal peptide catalyst. J. Am. Chem. Soc. 2010, 132, 15459-15501. Link

37. Schmidt, E.W. The hidden diversity of ribosomal peptide products. BMC Biol. 2010, 8, 83. Link

36. McIntosh, J.A.; Schmidt, E.W. Marine molecular machines: Heterocyclization in cyanobactin biosynthesis. ChemBioChem 2010, 11, 1413-1421. Link

35. Tawfik, K.A.; Jeffs, P.; Bray, B.; Dubay, G.; Falkinham, J.O.; Mesbah, M.; Youssef, D.; Khalifa, S.; Schmidt, E.W. Burkholdines 1097 and 1229, potent antifungal agents from Burkholderia ambifaria 2.2N. Org. Lett. 2010, 12, 664-666. Link

34. McIntosh, J.; Donia, M.S.; Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 2010, 132, 4089-4091. Link

33. Hirose, E.; Neilan, B.A.; Schmidt, E.W.; Murakami, A. Enigmatic Life and Evolution of Prochloron and Related Cyanobacteria Inhabiting Colonial Ascidians. In: Handbook on Cyanobacteria: Biochemistry, Biotechnology and Applications. 2010.

32. Schmidt, E.W; Donia, M.S. Cyanobactins, ubiquitous cyanobacterial metabolites.  In: Comprehensive Natural Products II. 2010.

2009

31. Brady, S.; Simmons, L.; Kim, J.H.; Schmidt, E.W. Metagenomic approaches to natural products from free-living and symbiotic organisms. Nat. Prod. Rep. 2009, 26, 1488-14503. Link

30. Peraud, O.; Biggs, J.S; Hughen, R.W.; Light, A.; Concepcion, G.P.; Olivera, B.M.; Schmidt, E.W. Microhabitats within venomous cone snails yield diverse actinobacteria. Appl. Environ. Microbiol. 2009, 75, 6820-6826. Link

29. Yang, J.C.; Madupu, R.; Durkin, A.S.; Ekborg, N.A.; Pedamallu, C.S.; Hostetler, J.B.; Radune, D.; Toms, B.S.; Henrissat, B.; Coutinho, P.M.; Schwarz, S.; Field, L.; Trindade-Silva, A.E.; Soares, C.A.; Elshahawi, S.; Hanora, A.; Schmidt, E.W.; Haygood, M.G.; Posfai, J.; Benner, J.; Madinger, C.; Nove, J.; Anton, B.; Chaudhary, K.; Foster, J.; Holman, A.; Kumar, S.; Lessard, P.A.; Luyten, Y.A.; Slatko, B.; Wood, N.; Wu, B.; Teplitski, M.; Mougous, J.D.; Ward, N.; Eisen, J.A.; Badger, J.H.; Distel, D.L. The complete genome of Teredinibacter turnerae T7901: an intracellular endosymbiont of marine wood-boring bivalves (shipworms). PLoS One 2009 1;4, e6085. Link

28. Schmidt, E.W.; Donia, M.S. Cyanobactin ribosomal peptides — a case of deep metagenome mining. Methods Enzymol. 2009 458, 575-596. Link

27. Lee, J.; McIntosh, J.; Hathaway, B.; Schmidt, E.W. Using marine natural products to discover a protease that catalyzes peptide macrocyclization of diverse substrates. J. Am. Chem. Soc. 2009, 131, 2122-2124. Link

26. McIntosh, J.A.; Donia, M.S.; Schmidt, E.W. Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat. Prod. Rep. 2009, 26, 537-559. Link

25. Schmidt, E.W. Bacterial chemical defenses in animal hosts. In: Defensive Mutualism in Microbial Symbiosis. 2009.

2004-2008

24. Schmidt, E.W. Trading molecules and tracking targets in symbiotic interactions. Nat. Chem. Biol.2008, 4, 466-473. Link

23. Donia, M.S.; Ravel, J.; Schmidt, E.W. A global assembly line for cyanobactins. Nat. Chem. Biol.2008, 4,341-343. Link

22. Sims, J.W.; Schmidt E.W. Thioesterase-like role for fungal PKS-NRPS hybrid reductive domain. J. Am. Chem. Soc. 2008, 130, 11149-11155. Link

21. Nelson, J.T.; Lee, J.; Sims, J.W.; Schmidt, E.W. Characterization of SafC, a catechol 4-O-methyltransferase involved in saframycin biosynthesis. Appl. Environ. Microbiol. 2007, 73, 3575-3580. Link

20. Donia, M.; Hathaway, B.J.; Sudek, S.; Haygood, M.G.; Rosovitz, M.J.; Ravel, J.; Schmidt, E.W. Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nat. Chem. Biol. 2006, 2, 729-735. Link

19. Sudek, S.; Haygood, M.G.; Youssef, D.T.A.; Schmidt, E.W. Structure of trichamide, a cyclic peptide from the bloom-forming bacterium Trichodesmium erythraeum, predicted from the genome sequence. Appl. Environ. Microbiol. 2006, 72, 4382-4387. Link

18. Schmidt, E.W.; Nelson, J.T.;  Rasko, D.A.; Sudek, S.; Eisen, J; Haygood, M.G.; Ravel, J. Patellamide   A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the obligate cyanobacterial  symbiont of Lissoclinum patella. Proc. Natl. Acad. Sci. USA 2005, 102, 7315-7320. Link

17. Schmidt, E.W. From chemical structure to environmental biosynthetic pathways: navigating marine
invertebrate-bacteria associations. Trends Biotechnol. 2005, 23, 437-440. Link

16. Sims, J.W.; Fillmore, J.P.; Warner, D.D.; Schmidt, E.W. Equisetin biosynthesis in Fusarium
heterosporum. Chem. Commun. 2005, 186-188. Link

15. Schmidt, E.W.; Sudek, S.; Haygood, M.G. Genetic evidence supports secondary metabolic diversity in
Prochloron spp., the cyanobacterial symbiont of a tropical ascidian. J. Nat. Prod. 2004, 67, 1341-1345. Link

14. Schmidt, E.W.; Nelson, J.T.; Fillmore, J.P. Synthesis of tyrosine derivatives for saframycin MX1
biosynthetic studies. Tetrahedron Lett., 2004, 45, 3921-3924. Link

13. Schmidt, E.W.; Raventos-Suarez, C.; Bifano, M.; Menendez, A.T.; Fairchild, C.; Faulkner, D.J.
Scleritodermin A, a cytotoxic peptide from the lithistid sponge, Scleritoderma nodosum.  J. Nat. Prod. 2004, 67, 475-478. Link

EWS Grad/Postdoc

12. Hitchman, T.S.;* Schmidt, E.W.;* Rarick, M.A.; Linz, J.E.; Townsend, C.A. Hexanoate synthase, a
   specialized type I fatty acid synthase in aflatoxin B1 biosynthesis. Bioorganic Chem. 2001, 29, 293-307. Link

*contributed equally

11. Haygood, M.G.; Schmidt, E.W.; Davidson, S.K.; Faulkner, D.J. Microbial symbionts of marine
invertebrates: Opportunities for microbial biotechnology. In: Molecular Marine Microbiology, D.
Bartlett, ed. Horizon Scientific Press, 2000.

10. Faulkner, D.J.; Harper, M.K.; Salomon, C.E.; Schmidt, E.W. Symbiotic bacteria in sponges:
Sources of bioactive compounds. In: Drugs from the Sea, N. Fusetani, ed, Karger, New York, 2000. Link

9.  Schmidt, E.W.; Obraztsova, A.Y.; Davidson, S.K.; Faulkner, D.J.; Haygood, M.G. The peptide
containing symbiont of the marine sponge Theonella swinhoei is a novel d-proteobacterium,
Candidatus Entotheonella palauensis.” Mar. Biol. 2000, 136, 969-977. Link

8. Haygood, M.G.; Schmidt, E.W.; Davidson, S.K.; Faulkner, D.J. Microbial Symbionts of Marine
Invertebrates: Opportunities for Microbial Biotechnology. J. Mol. Microbiol. Biotechnol. 1999, 1, 33-34. Link

7. Faulkner, D.J.; Harper, M.K.; Salomon, C.E.; Schmidt, E.W. Localization of bioactive metabolites
in marine sponges. Proceedings, 5th International Sponge Symposium, Brisbane, Australia. Memoirs of
the Queensland Museum. 1999, 44, 167-173.

6.  Schmidt, E.W.; Faulkner, D.J. Microsclerodermins C-E, antifungal cyclic peptides from the lithistid
sponges Theonella sp. and Microscleroderma sp. Tetrahedron, 1998, 54, 3043-3056. Link

5.  Schmidt, E.W.; Bewley, C.A.; Faulkner, D.J. Theopalauamide, a bicyclic glycopeptide from
filamentous bacterial symbionts of the lithistid sponge Theonella swinhoei from Palau and Mozambique.
J. Org. Chem. 1998, 63, 1254-1258. Link

4.  Schmidt, E.W.; Harper, M.K.; Faulkner, D.J. Mozamides A and B, cyclic peptides from a Theonellid
sponge from Mozambique. J. Nat. Prod. 1997, 60, 779-782. Link

3.  Schmidt, E.W.; Faulkner, D.J. Absolute configuration of methyl (2Z,6R,8R,9E)-3,6-epoxy-4,6,8
triethyl-2,4,9-dodecatrienoate from the sponge Plakortis halichondrioides. Tetrahedron Lett. 1996, 37,
6681-6684. Link

2.  Schmidt, E.W.; Faulkner, D.J. Palauolol, a new anti-inflammatory sesterterpene from the sponge
Fascaplysinopsis sp. from Palau. Tetrahedron Lett. 1996, 37, 3951-3954. Link

1.  Schmidt, E.W.; Harper, M.K.; Faulkner, D.J. Makaluvamines H-M and damirone C from the Pohnpeian sponge Zyzzya fuliginosa. J. Nat. Prod. 1995, 58, 1861-1867. Link

 

Upcoming Events

View Calendar

IT Services

CPCSS - COMPUTER SUPPORT REQUEST

COMPUTER SUPPORT REQUEST