Michael Burkart
Natural product synthesis/biosynthesis, Biological chemistry and enzymology, Metabolic engineering.
Natural product synthesis/biosynthesis, Biological chemistry and enzymology, Metabolic engineering.
Contact Information
Professor of Chemistry and Biochemistry
Office: Pacific Hall 6100D
Phone: 858-534-5673
Email: mburkart@ucsd.edu
Web: http://burkartlab.ucsd.edu
Group: View group members
Office: Pacific Hall 6100D
Phone: 858-534-5673
Email: mburkart@ucsd.edu
Web: http://burkartlab.ucsd.edu
Group: View group members
Education
1999 Ph.D., Organic Chemistry, Scripps Research Institute
1994 B.A., Chemistry, Rice University
1999 Ph.D., Organic Chemistry, Scripps Research Institute
1994 B.A., Chemistry, Rice University
Appointments
2000 N.I.H., , Harvard Medical School
2000 N.I.H., , Harvard Medical School
Awards and Academic Honors
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: Proteomic 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: Compact Disc - Based Molecular Diagnostics
The third project in the lab is the development of inexpensive screens for the quantitative and qualitative analysis of biomolecular species. We have introduced a new technology to detect biomolecular interactions using a standard compact disc (CD) and CD player. This work has gained broad scientific and popular interest. We are currently exploring additional biomolecular species (DNA, RNA, carbohydrates, and peptides) for identification with this system. We have demonstrated how a digital architecture can inherently benefit biomolecular assays because of direct interaction with digital algorithms. Currently, we are programming self-executing assays using artificially intelligent algorithms that allow unskilled users to perform complex assays and deliver results to trained professionals via conventional digital networks. We are also improving the chemistry of polycarbonate surface modification to be applicable to production scales. We believe that this technology could revolutionize the way molecules are visualized and understood by non-scientists.
Project 4: Biofuels 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.
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: Compact Disc - Based Molecular Diagnostics
The third project in the lab is the development of inexpensive screens for the quantitative and qualitative analysis of biomolecular species. We have introduced a new technology to detect biomolecular interactions using a standard compact disc (CD) and CD player. This work has gained broad scientific and popular interest. We are currently exploring additional biomolecular species (DNA, RNA, carbohydrates, and peptides) for identification with this system. We have demonstrated how a digital architecture can inherently benefit biomolecular assays because of direct interaction with digital algorithms. Currently, we are programming self-executing assays using artificially intelligent algorithms that allow unskilled users to perform complex assays and deliver results to trained professionals via conventional digital networks. We are also improving the chemistry of polycarbonate surface modification to be applicable to production scales. We believe that this technology could revolutionize the way molecules are visualized and understood by non-scientists.
Project 4: Biofuels 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
Organic Chemistry
Interdisciplinary interests
Bioorganic
Synthesis
Macromolecular Structure
Synthesis
Macromolecular Structure
Image Gallery
Selected Publications
- Jones BD, La Clair JJ, Moore CE, Rheingold AL, Burkart MD, "Convergent route to the spirohexenolide macrocycle.", Org Lett, 2010, 20, 4516-9 [View Abstract]
- Reyes CP, La Clair JJ, Burkart MD, "Metabolic probes for imaging endosymbiotic bacteria within toxic dinoflagellates.", Chem Commun (Camb), 2010, 43, 8151-3 [View Abstract]
- Foley TL, Young BS, Burkart MD, "Phosphopantetheinyl transferase inhibition and secondary metabolism.", FEBS J, 2009, 23, 7134-45 [View Abstract]
- Hur GH, Meier JL, Baskin J, Codelli JA, Bertozzi CR, Marahiel MA, Burkart MD, "Crosslinking studies of protein-protein interactions in nonribosomal peptide biosynthesis.", Chem Biol, 2009, 4, 372-81 [View Abstract]
- Kang M, Jones BD, Mandel AL, Hammons JC, DiPasquale AG, Rheingold AL, La Clair JJ, Burkart MD, "Isolation, structure elucidation, and antitumor activity of spirohexenolides A and B.", J Org Chem, 2009, 23, 9054-61 [View Abstract]
- Kang M, Jones BD, Mandel AL, Hammons JC, DiPasquale AG, Rheingold AL, La Clair JJ, Burkart MD, "Isolation, structure elucidation, and antitumor activity of spirohexenolides A and B.", J Org Chem, 2009, 23, 9054-61 [View Abstract]
- Meier JL, Burkart MD, "The chemical biology of modular biosynthetic enzymes.", Chem Soc Rev, 2009, 7, 2012-45 [View Abstract]
- Meier JL, Niessen S, Hoover HS, Foley TL, Cravatt BF, Burkart MD, "An orthogonal active site identification system (OASIS) for proteomic profiling of natural product biosynthesis.", ACS Chem Biol, 2009, 11, 948-57 [View Abstract]
- Meier JL, Niessen S, Hoover HS, Foley TL, Cravatt BF, Burkart MD, "An orthogonal active site identification system (OASIS) for proteomic profiling of natural product biosynthesis.", ACS Chem Biol, 2009, 11, 948-57 [View Abstract]