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Dr. Bradley Moore
Bradley S. Moore, Ph.D.
Skaggs School of Pharmacy and Pharmaceutical Sciences Professor
Scripps Institution of Oceanography
Research Summary: Natural Product Engineering
Dr. Moore's laboratory is focused on understanding the fundamental mechanisms and pathways involved in how bacteria 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 bacteria, which harbor promising natural product compounds such as the potent anticancer agents salinosporamide A and didemnin, the polyketide antibiotics enterocin and marinopyrrole, and the cyclomarin anti-inflammatory peptides.
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 marine bacteria 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); Chair of the Natural Product Reports Editorial Board (2011-present); 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).
- 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).
Key Contributions to Pharmaceutical Sciences
- Pioneered the biosynthesis and bioengineering of marine bacterial natural product drugs.
- Sequenced and characterized the first complete marine actinomycete genomes.
- Developed metabolic engineering and synthetic biology techniques for the rational production of new chemical entities.
- Discovered antibiotic biosynthesis enzymes and elucidated their mechanistic enzymology.
Selected Recent Publications (from >150 peer- reviewed articles)
- 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
Potential Collaborative Programs with the Pharmaceutical Industry
- 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.