Burkart, Michael
Natural product synthesis/biosynthesis, Biological chemistry and enzymology, Metabolic engineering.

Contact Information
Professor, Department of Chemistry and Biochemistry
Associate Director, California Center for Algae Biotechnology

Office: Pacific Hall 6100D
Phone: 858-534-5673
Email: mburkart@ucsd.edu
Web: burkartlab.ucsd.edu
Group: View group members
Education
1999 Ph.D., Organic Chemistry, Scripps Research Institute
1994 B.A., Chemistry, Rice University
Appointments
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
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: Chemical Biology Tools for Natural Product Biosynthetic Pathways

We focus on polyketide (PK) and non-ribosomal peptide (NRP) synthases in the development of small-molecule probes to guide metabolic engineering and discover natural product systems. We began by probing the carrier protein domain essential to all PK, NRP, and fatty acid biosyntheses. Using fluorescent and affinity reporters, we are able to visualize, isolate, and manipulate carrier protein domains from natural and engineered pathways. Using this methodology, we have created a general profiling system via multiplex analysis of fluorescent substrates that offers a unique classification scheme for carrier protein domains within NRPS and PKS synthases. We are currently developing molecules to target other domains within modular synthases and envision a set of domain specific markers for each stage in PK and NRP biosynthesis. We anticipate that all of these tools will serve as diagnostic reporters for metabolic engineering, visualization probes for natural product discovery, and as potential antibiotics against virulence factor-producing pathogens.

Project 2: Chemical Direction of Coenzyme A Biosynthesis

Our natural product research led us into the investigation of coenzyme A (CoA) biosynthesis and analog design. We have developed new synthetic techniques to synthesize analogs of CoA precursors, pantetheine and phosphopantetheine, in an effort to design novel CoA analogs to understand functional requirements of CoA-dependent enzymes. This has led us to study the enzymes involved in CoA biosynthesis and the chemo-enzymatic synthesis of coenzyme A analogs in vitro and in vivo. Here, we found that pantetheine analogs may be incubated with cell culture, where uptake and metabolic transformation into labeled CoA analogs via takes place. This pathway may be used to deliver reporter molecules or selective inhibitors of CoA-dependent enzymes to intracellular locations. This scheme also works well in vitro. Our efforts have forwarded what is arguably one of the most versatile tools for multifunctional protein labeling, including bio-orthogonal reactive probes that can be applied to a variety of in vivo applications. We have also adapted this biosynthetic access to rare analogs to prepare tailored probes for the mechanistic examination of CoA-driven biosynthesis. Here we can visualize protein-protein interactions via covalent protein attachment of transition-state designed inhibitors. This technique introduces a powerful new tool to probe the structural biology of biosynthetic enzymes.

Project 3: Biofuels and products from Algae

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 biofuel production. Using the proteomic tools developed for modular synthases, we perform activity, structural, and engineering studies in single-cellular algae.
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)
Image Gallery


As part of the California Center for Algae Biotechnology (Cal-CAB) our group has made important contributions to algae metabolic engineering, culture, and product conversion of algae biomass.

The study of natural product biosynthesis, including fatty acid, polyketide, and non-ribosomal peptide pathways, are a central theme in our laboratory. We have developed a suite of chemo-enzymatic tools to study and engineer these pathways, enabling synthetic biology of these systems.


Our group is also interested in natural product anticancer agents. Our research into the synthesis and biosynthesis of the pladienolides and FD-895 has uncovered the most potent anticancer spliceosome inhibitors to date.
Selected Publications