Burkart, Michael
Natural product synthesis/biosynthesis, Biological chemistry and enzymology, Metabolic engineering.
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
Teddy Traylor Faculty Scholar
Office: Pacific Hall 6100A
Phone: 858-534-5673
Email: mburkart@ucsd.edu
Web: burkartlab.ucsd.edu
Group: View group members
Accepting Rotation Students: Yes
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
Accepting Rotation Students: Yes
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
2023- Chair, UCSD Department of Chemistry and Biochemistry
2017-2019 Vice Chair, UCSD Department of Chemistry and Biochemistry
2012- Professor, UCSD Department of Chemistry and Biochemistry
2008-2012 Associate Professor, UCSD Department of Chemistry and Biochemistry
2002-2008 Assistant Professor, UCSD Department of Chemistry and Biochemistry
2000-2002 NIH Postdoctoral Fellow, Harvard Medical School
2023- Chair, UCSD Department of Chemistry and Biochemistry
2017-2019 Vice Chair, UCSD Department of Chemistry and Biochemistry
2012- Professor, UCSD Department of Chemistry and Biochemistry
2008-2012 Associate Professor, UCSD Department of Chemistry and Biochemistry
2002-2008 Assistant Professor, UCSD Department of Chemistry and Biochemistry
2000-2002 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
2017
Fellow, American Association for the Advancement of Science (AAAS)
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.
The modular metabolic pathways encoding fatty acid synthases (FASs), polyketide synthases (PKSs), and non-ribosomal peptide synthetases (NRPSs) offer a glimpse of how Nature’s evolution of an iterative multienzyme pathway can diverge into the impressive pharmacopeia of natural products observed at sea and on land. Unraveling the molecular logic of these pathways lies at the forefront of modern molecular science, and a major research topic of our lab, in line with our long-term objective of engineering these pathways for the preparation of novel compounds. Our most recent work has focused on leveraging chemical biology tools for the structural elucidation of these pathways. This has included NMR, x-ray crystallography, and cryo-EM methodologies to unravel pathway processivity and protein-protein interactions.
Project 2: Renewable and biodegradable fuels and materials from algae
Plastics have become omnipresent on the planet, and global plastics use is predicted to grow over the next 30 years, and petroleum consumption for plastics is expected to prevail over any decreases in petroleum consumption from adoption of renewable energy. Critically, plastics have become a major source of world pollution, especially in the ocean gyres, known as the ocean garbage patches. After working on algae biofuels for 10 years, we began to develop polyurethanes (PUs) made from algae feedstocks in 2018. Versatile, functional, and essential components of many products from shoes to furniture, PUs unfortunately also represent a major and ubiquitous plastic pollutant. Not only did we develop a path to produce PU foams from renewable algae biomass materials, but we have demonstrated their ability to be completely biodegradable under standard compost conditions. Here we see a key opportunity to meaningfully address non-biodegradable plastic pollution by development of a monomer recycling platform for polyester PUs. These polymers contain urethane bonds susceptible to chemical and enzymatic cleavage, making them one of the few plastics that can potentially be decomposed either by biodegradation, or by depolymerization and recycling of constitutive parts. Our discoveries have been incorporated into a spin-off company, Algenesis Materials, which is actively manufacturing renewable materials for applications in consumer products.
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. Most recently our group has focused both on the development of spliceosome modulators as potential anticancer drugs and on the development of proteolysis-targeting chimeras (PROTACs) for drug discovery tools. Our group has been a leader in the development of spliceosome modulators as potential clinical entries for blood-born malignancies and solid tumors. Our early work in 2007 set the stage for the structure elucidation pladienolide B and chemical synthesis of FD-895. This led to the development of a potent non-natural analog, 17S-FD-895, recently renamed Rebecsinib. Rebecsinib recently completed preclinical development, and we will soon be submitting an application to the FDA for an investigational new drug (IND) in order to begin clinical trials through a spin-off company Aspera Biomedicines.
The modular metabolic pathways encoding fatty acid synthases (FASs), polyketide synthases (PKSs), and non-ribosomal peptide synthetases (NRPSs) offer a glimpse of how Nature’s evolution of an iterative multienzyme pathway can diverge into the impressive pharmacopeia of natural products observed at sea and on land. Unraveling the molecular logic of these pathways lies at the forefront of modern molecular science, and a major research topic of our lab, in line with our long-term objective of engineering these pathways for the preparation of novel compounds. Our most recent work has focused on leveraging chemical biology tools for the structural elucidation of these pathways. This has included NMR, x-ray crystallography, and cryo-EM methodologies to unravel pathway processivity and protein-protein interactions.
Project 2: Renewable and biodegradable fuels and materials from algae
Plastics have become omnipresent on the planet, and global plastics use is predicted to grow over the next 30 years, and petroleum consumption for plastics is expected to prevail over any decreases in petroleum consumption from adoption of renewable energy. Critically, plastics have become a major source of world pollution, especially in the ocean gyres, known as the ocean garbage patches. After working on algae biofuels for 10 years, we began to develop polyurethanes (PUs) made from algae feedstocks in 2018. Versatile, functional, and essential components of many products from shoes to furniture, PUs unfortunately also represent a major and ubiquitous plastic pollutant. Not only did we develop a path to produce PU foams from renewable algae biomass materials, but we have demonstrated their ability to be completely biodegradable under standard compost conditions. Here we see a key opportunity to meaningfully address non-biodegradable plastic pollution by development of a monomer recycling platform for polyester PUs. These polymers contain urethane bonds susceptible to chemical and enzymatic cleavage, making them one of the few plastics that can potentially be decomposed either by biodegradation, or by depolymerization and recycling of constitutive parts. Our discoveries have been incorporated into a spin-off company, Algenesis Materials, which is actively manufacturing renewable materials for applications in consumer products.
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. Most recently our group has focused both on the development of spliceosome modulators as potential anticancer drugs and on the development of proteolysis-targeting chimeras (PROTACs) for drug discovery tools. Our group has been a leader in the development of spliceosome modulators as potential clinical entries for blood-born malignancies and solid tumors. Our early work in 2007 set the stage for the structure elucidation pladienolide B and chemical synthesis of FD-895. This led to the development of a potent non-natural analog, 17S-FD-895, recently renamed Rebecsinib. Rebecsinib recently completed preclinical development, and we will soon be submitting an application to the FDA for an investigational new drug (IND) in order to begin clinical trials through a spin-off company Aspera Biomedicines.
Primary Research Area
Organic Chemistry
Organic Chemistry
Interdisciplinary interests
Bioorganic
Synthesis
Macromolecular Structure
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)
• 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
We have developed a path to produce fuels and plastics from renewable algae biomass and have focused on making fully biodegradable materials, making them one of the few commercially viable plastics that can be made from 100% renewable monomers and can be decomposed either by biodegradation, or by de
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 actively developing new drugs, with a focus on natural product anticancer agents. Our research into the synthesis and biosynthesis of the pladienolides and FD-895 has uncovered Rebecsinib, the most potent anticancer spliceosome inhibitor to date.
We have developed a path to produce fuels and plastics from renewable algae biomass and have focused on making fully biodegradable materials, making them one of the few commercially viable plastics that can be made from 100% renewable monomers and can be decomposed either by biodegradation, or by de
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 actively developing new drugs, with a focus on natural product anticancer agents. Our research into the synthesis and biosynthesis of the pladienolides and FD-895 has uncovered Rebecsinib, the most potent anticancer spliceosome inhibitor to date.
Selected Publications See https://pubs.rsc.org/en/content/articlelanding/2020/gc/d0gc00852d
- Chen A,Re RN,Davis TD,Tran K,Moriuchi YW,Wu S,La Clair JJ,Louie GV,Bowman ME,Clarke DJ,Mackay CL,Campopiano DJ,Noel JP,Burkart MD "Visualizing the Interface of Biotin and Fatty Acid Biosynthesis through SuFEx Probes.", J Am Chem Soc, 2024, Vol. 146, Issue 2, 1388-1395 [View]
- Sztain T,Corpuz JC,Bartholow TG,Sanlley Hernandez JO,Jiang Z,Mellor DA,Heberlig GW,La Clair JJ,McCammon JA,Burkart MD "Interface Engineering of Carrier-Protein-Dependent Metabolic Pathways.", ACS Chem Biol, 2023, Vol. 18, Issue 9, 2014-2022 [View]
- Gunawan NR,Tessman M,Zhen D,Johnson L,Evans P,Clements SM,Pomeroy RS,Burkart MD,Simkovsky R,Mayfield SP "Biodegradation of renewable polyurethane foams in marine environments occurs through depolymerization by marine microorganisms.", Sci Total Environ, 2022, Vol. 850, 158761 [View]
- Mindrebo JT,Chen A,Kim WE,Re RN,Davis TD,Noel JP,Burkart MD "Structure and mechanistic analyses of the gating mechanism of elongating ketosynthases.", ACS Catal, 2021, Vol. 11, Issue 12, 6787-6799 [View]
- Du D,Katsuyama Y,Horiuchi M,Fushinobu S,Chen A,Davis TD,Burkart MD,Ohnishi Y "Structural basis for selectivity in a highly reducing type II polyketide synthase.", Nat Chem Biol, 2020, Vol. 16, Issue 7, 776-782 [View]
- Mindrebo JT,Patel A,Kim WE,Davis TD,Chen A,Bartholow TG,La Clair JJ,McCammon JA,Noel JP,Burkart MD "Gating mechanism of elongating β-ketoacyl-ACP synthases.", Nat Commun, 2020, Vol. 11, Issue 1, 1727 [View]
- Misson LE,Mindrebo JT,Davis TD,Patel A,McCammon JA,Noel JP,Burkart MD "Interfacial plasticity facilitates high reaction rate of E. coli FAS malonyl-CoA:ACP transacylase, FabD.", Proc Natl Acad Sci U S A, 2020, Vol. 117, Issue 39, 24224-24233 [View]
- Phung Hai TA, De Backer LJ, Cosford ND, Burkart MD. "Preparation of mono-and diisocyanates in flow from renewable carboxylic acids.", Organic Process Research Development, 2020, Vol. 24, 2342-6
- 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 [View]
- 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 [View]
- Pachiadaki MG,Brown JM,Brown J,Bezuidt O,Berube PM,Biller SJ,Poulton NJ,Burkart MD,La Clair JJ,Chisholm SW,Stepanauskas R "Charting the Complexity of the Marine Microbiome through Single-Cell Genomics.", Cell, 2019, Vol. 179, Issue 7, 1623-1635.e11 [View]
- 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 [View]
- 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 [View]
- Michaud JM,Thompson LR,Kaul D,Espinoza JL,Richter RA,Xu ZZ,Lee C,Pham KM,Beall CM,Malfatti F,Azam F,Knight R,Burkart MD,Dupont CL,Prather KA "Taxon-specific aerosolization of bacteria and viruses in an experimental ocean-atmosphere mesocosm.", Nat Commun, 2018, Vol. 9, Issue 1, 2017 [View]
- 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 [View]
- Lin L,Nonejuie P,Munguia J,Hollands A,Olson J,Dam Q,Kumaraswamy M,Rivera H Jr,Corriden R,Rohde M,Hensler ME,Burkart MD,Pogliano J,Sakoulas G,Nizet V "Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens.", EBioMedicine, 2015, Vol. 2, Issue 7, 690-8 [View]
- Beld J,Sonnenschein EC,Vickery CR,Noel JP,Burkart MD "The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life.", Nat Prod Rep, 2014, Vol. 31, Issue 1, 61-108 [View]
- 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 [View]
- Kohli RM,Walsh CT,Burkart MD "Biomimetic synthesis and optimization of cyclic peptide antibiotics.", Nature, 2002, Vol. 418, Issue 6898, 658-61 [View]