Burkart, Michael
Natural product synthesis/biosynthesis, Biological chemistry and enzymology, Metabolic engineering.
Education
1999 Ph.D.,
Organic Chemistry,
Scripps Research Institute
1994 B.A.,
Chemistry,
Rice University
Appointments
2017 Vice Chair,
UCSD Department of Chemistry and Biochemistry
2011 Professor,
UCSD Department of Chemistry and Biochemistry
2008 Associate Professor,
UCSD Department of Chemistry and Biochemistry
2002 Assistant Professor,
UCSD Department of Chemistry and Biochemistry
2000 NIH Postdoctoral Fellow,
Harvard Medical School
Awards and Academic Honors
2019
Chancellor's Award for Excellence in Postdoctoral Scholar Mentoring
2017
Teddy Traylor Faculty Scholar
2015
Fellow, Royal Society of Chemistry (FRSC)
2010
Organic and Biomolecular Chemistry Lecture Award
2007
Alfred P. Sloan Fellowship
2006
American Cancer Society Research Scholar
2004
National Science Foundation CAREER Award
2004
Hellman Fellow
2003
Ellison Medical Foundation, New Scholar Award in Global Infectious Disease
1999-2002
NIH Postdoctoral Fellowship
1998
Bristol-Myers Squibb Graduate Fellowship
1994
Zevi & Bertha Salsburg Award for Excellence in Chemistry
Research Interests
Project 1: Biosynthetic chemical and structural biology.
Beginning in 2002, we launched a program to develop a comprehensive toolbox to address biosynthetic enzyme function through small molecule probes. We began by preparing synthetic analogs to decorate the ACP in these pathways, with plans to expand into understanding the interactions between ACP and cognate catalytic proteins. Our first work focused on modifying carrier proteins through the use of the permissive post-translational modification enzyme, 4’-phosphopantetheinyltransferase (PPTase), which effectively transferred synthetic probes onto the 4’-phosphopantetheine arm. This replaced natural substrates with compounds we designed, and for which we developed a synthetic pathway to prepare. These tools were readily adopted by a majority of the field – today most groups that study PKS or NRPS pathways in vitro use our fluorescent carrier protein labeling methodology as a tool to identify and track these proteins. As our program developed, we realized that our designs could be expanded to selectively probe protein•protein interactivity. We have continued to develop these tools, improving them for routine use, including methods to reversibly label ACPs, and adapting them to study domain-selective enzymatic functions. Given the modular nature of NRPS and PKS pathways, there still exist many enzyme targets for the development of probes. We now have a fully functional toolset with which to understand these molecular events, and we have begun to unravel the molecular code that regulates reactivity and processivity through these modular pathways.
Project 2: Metabolic engineering and renewable fuels/materials.
We have also demonstrated that the application of these tools is critical to guide metabolic engineering (or synthetic biology), highlighting the importance of matching protein•protein interactions. The Burkart lab has played a major role in the creation of the San Diego Center for Algae Biotechnology (SD-CAB). We are currently involved in the study of algal metabolic pathways with an emphasis upon engineering improved biofuels and renewable monomers for material applications. Using the tools we have developed for modular synthases, we perform activity, structural, and engineering studies on pathways within single-cellular algae.
Project 3: Drug discovery and medicinal chemistry.
In addition to biosynthetic work, a portion of our laboratories resources have been devoted to the drug discovery and development efforts. Here, we have recently developed highly collaborative programs in infectious disease and cancer. We have been at the forefront of chemical synthesis and medicinal chemistry and have through strong collaborations at UC San Diego’s Moores Cancer Center advanced a new understanding for the target and timing of splice modulation. We have also developed strong collaborations for virtual approaches to guide the development of next generation leads. These have established our ability to rapidly integrate and tackle key problems associated with the translation of therapeutics for infectious diseases.
Primary Research Area
Organic Chemistry
Interdisciplinary interests
Bioorganic
Synthesis
Macromolecular Structure
Outreach Activities
• Co-Founder and regular participant, Natural Product Affinity Group (NPAG)
• Co-Founder and Associate Director, California Center for Algae Biotechnology (Cal-CAB)
• Co-organizer, EDGE (Educating and Developing Workers for the Green Economy)
• Guest lecturer/presenter, various community venues (San Diego Rotary Club, Fleet Science Center, Two Scientists Walk into a Bar, Coronado Round Table)
Selected Publications
See
https://scholar.google.com/citations?hl=en&user=I2JhdYQAAAAJ&view_op=list_works&sortby=pubdate
- Charov K,Burkart MD "A single tool to monitor multiple protein-protein interactions of the Escherichia coli acyl carrier protein.", ACS Infect Dis, 2019,
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- Davis TD,Michaud JM,Burkart MD "Active site labeling of fatty acid and polyketide acyl-carrier protein transacylases.", Org Biomol Chem, 2019, Vol. 17, Issue 19, 4720-4724
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- Dodge GJ,Patel A,Jaremko KL,McCammon JA,Smith JL,Burkart MD "Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli.", Proc Natl Acad Sci U S A, 2019, Vol. 116, Issue 14, 6775-6783
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- Milligan JC,Lee DJ,Jackson DR,Schaub AJ,Beld J,Barajas JF,Hale JJ,Luo R,Burkart MD,Tsai SC "Molecular basis for interactions between an acyl carrier protein and a ketosynthase.", Nat Chem Biol, 2019, Vol. 15, Issue 7, 669-671
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- Sztain T,Patel A,Lee DJ,Davis TD,McCammon JA,Burkart MD "Modifying the Thioester Linkage Affects the Structure of the Acyl Carrier Protein.", Angew Chem Int Ed Engl, 2019, Vol. 58, Issue 32, 10888-10892
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- Konno S,La Clair JJ,Burkart MD "Trapping the Complex Molecular Machinery of Polyketide and Fatty Acid Synthases with Tunable Silylcyanohydrin Crosslinkers.", Angew Chem Int Ed Engl, 2018, Vol. 57, Issue 52, 17009-17013
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- Roulet J,Taton A,Golden JW,Arabolaza A,Burkart MD,Gramajo H "Development of a cyanobacterial heterologous polyketide production platform.", Metab Eng, 2018, Vol. 49, 94-104
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- Sarria S,Bartholow TG,Verga A,Burkart MD,Peralta-Yahya P "Matching Protein Interfaces for Improved Medium-Chain Fatty Acid Production.", ACS Synth Biol, 2018, Vol. 7, Issue 5, 1179-1187
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- Tallorin L,Wang J,Kim WE,Sahu S,Kosa NM,Yang P,Thompson M,Gilson MK,Frazier PI,Burkart MD,Gianneschi NC "Discovering de novo peptide substrates for enzymes using machine learning.", Nat Commun, 2018, Vol. 9, Issue 1, 5253
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- León B,Kashyap MK,Chan WC,Krug KA,Castro JE,La Clair JJ,Burkart MD "A Challenging Pie to Splice: Drugging the Spliceosome.", Angew Chem Int Ed Engl, 2017, Vol. 56, Issue 40, 12052-12063
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- Kumar D,Kashyap MK,La Clair JJ,Villa R,Spaanderman I,Chien S,Rassenti LZ,Kipps TJ,Burkart MD,Castro JE "Selectivity in Small Molecule Splicing Modulation.", ACS Chem Biol, 2016, Vol. 11, Issue 10, 2716-2723
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- Nguyen C, Haushalter RW, Lee DJ, Markwick PR, Bruegger J, Caldara-Festin G, Finzel K, Jackson DR, Ishikawa F, O'Dowd B, McCammon JA, Opella SJ, Tsai SC, Burkart MD, "Trapping the dynamic acyl carrier protein in fatty acid biosynthesis.", Nature, 2014, Vol. 505, Issue 7483, 427-31
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