Natural Product Engineering
Skaggs School of Pharmacy and Pharmaceutical Sciences Professor
Scripps Institution of Oceanography
Dr. Moore's laboratory is focused on understanding the fundamental mechanisms and pathways involved in how microbes produce antibiotics, anticancer agents, and other bioactive natural products, with a special emphasis on marine microorganisms. Research is performed at the chemistry-biology interface and involves a number of sophisticated approaches that include heterologous biosynthesis, mutasynthesis, chemoenzymatic total synthesis, genome mining, and in vitro and in vivo biochemical analysis. Biosynthetic systems are largely targeted from marine microbes, which harbor promising natural product compounds such as the potent anticancer agents salinosporamide A and didemnin, the polyketide antibiotics taromycin and marinopyrrole, and the neurotoxins domoic acid and kainic acid.
Microbial biodiversity remains one of the last great biotic frontiers, and developing effective strategies to discover and exploit new small molecules from this resource is integral to the success of future drug discovery efforts. The introduction of recombinant technology to the natural product discovery process has allowed us to interrogate and manipulate biosynthetic processes in order to expand the biosynthetic capabilities of microbes to yield new chemical entities for biological evaluation.
B.S. in Chemistry (1989) University of Hawaii; Ph.D. in Bioorganic Chemistry (1994) University of Washington.
Awards and Honors:
ASP Matt Suffness New Investigator Award (2001); NIH SBCB Study Section founding member (2005-8); Novartis-MIT Lecturer in Organic Chemistry (2009-10); Fellow of the Royal Society for Chemistry (2010); Chair of the Natural Product Reports Editorial Board (2011-2018); President of ASP (2013-2014); Chair of the 2014 Marine Natural Products GRC; ACS Arthur C. Cope Scholar Award (2013); ETH Visiting Faculty Award (2014). Fellow of the American Academy of Microbiology (2017); Novartis-UC Berkeley Lecturer in Organic Chemistry (2017); RSC Natural Product Chemistry Prize (2018); C. Richard Hutichinson Lectureship, University of Wisconsin (2019); Alexander M. Cruikshank Lecture Award in Chemistry, GRC on Marine Natural Products, 2019; Norman R. Farnsworth Research Achievement Award, American Society of Pharmacognosy, 2021.
- Contemporary Topics in Pharmacology (SPPS 218B).
- Pharmaceutical Chemistry (SPPS 221).
- Pharmaceutical Biochemistry (SPPS 223).
- Seminar in Marine Natural Products (SIO 262).
- Special Topics in Marine Natural Products (SIO 264).
- Pioneered the biosynthesis and bioengineering of marine natural product drug leads.
- Developed genome mining and synthetic biology techniques for the rational production of new antibiotic and anticancer drug leads.
- Discovered antibiotic biosynthesis and resistance enzymes and elucidated their mechanisms enzymology.
- Decoded the first harmful algal bloom neurotoxin.
- Kersten et al. (2011). A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat. Chem. Biol. 7:794-802.
- Xu et al. (2012). Bacterial biosynthesis and maturation of the didemnin anticancer agents. J. Am. Chem. Soc. 134:8625-8632.
- Teufel et al. (2013). Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Nature. 503:552-556.
- Agarwal V1 et al. (2014) Biosynthesis of polybrominated aromatic organic compounds by marine bacteria. Nat Chem Biol. 10(8):640-7
- Yamanaka et al. (2014). Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. PNAS. 111:1957-1962.
- Tang X1 et al. (2015) Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining. ACS Chem Biol. 10(12):2841-9
- El Gamal A et al. (2016) Biosynthesis of coral settlement cue tetrabromopyrrole in marine bacteria by a uniquely adapted brominase-thioesterase enzyme pair. Proc Natl Acad Sci U S A. 113(14):3797-802
- Brunson et al. (2018) Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science. 361:1356-1358.
- Luhavaya et al. (2019) Biosynthesis of L-4-chlorokynurenin, an antidepressant prodrug and a non-proteinogenic amino acid found in lipopeptide antibiotics. Angew. Chem. Int. Ed., 58:8394-8399.
- 20 years of experience in the discovery and application of natural products and their biosynthetic enzymes and genes.
- Broad array of chemical, biochemical and genetic approaches to understanding and bioengineering the biosynthesis of natural product drugs.