Professor, Department of Chemistry and Biochemistry
Associate Director, California Center for Algae Biotechnology
Teddy Traylor Faculty Scholar

Office: Pacific Hall 6100A
Phone: 858-534-5673
Email: mburkart@ucsd.edu
Web: burkartlab.ucsd.edu
Group: View group members

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

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.

Bioorganic
Synthesis
Macromolecular Structure

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.