About

Professor Michael D. Burkart is a faculty member in the Department of Chemistry and Biochemistry at the University of California, San Diego. His research focuses on natural product biosynthesis, protein-protein interactions, and the development of bioengineering tools for natural product discovery and modification. His work involves characterizing carrier protein interactions in glycoside natural products, as well as developing heterobifunctional small molecules such as PROTACs for targeted protein degradation. Additionally, his research includes the synthesis of natural product-based anti-cancer drug targets, the elucidation of biosynthetic pathways, and the engineering of biosynthetic enzymes for natural product production.

Research topics

• Chemistry
• Organic chemistry
• Biochemistry
• Computer Science
• Waste management
• Cell biology
• Stereochemistry
• Ecology
• Nanotechnology
• Computational biology
• Chemical engineering
• Biology
• Engineering
• Materials science
• Environmental science
• Combinatorial chemistry
• Genetics

Selected publications

• A Hidden Binding Pocket in the β- ketoacyl-ACP Synthase FabB

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-28

  articleOpen accessCorresponding

  ABSTRACT Assembly-line enzymes carry out multi-step synthesis of diverse metabolites by using a handful of catalytic motifs in which minor structural differences control substrate specificity and reaction order. Here we examine differences in substrate binding to FabB and FabF, the two β-ketoacyl-ACP synthases (KSs) responsible for fatty acid elongation in Escherichia coli , by exploring a peculiar mutational effect. In FabB, a blocking mutation in the acyl binding pocket yields a shifted, but broad product profile, while in FabF, the same mutation disrupts the binding of acyl chains longer than eight carbons (C8). X-ray crystal structures of the FabB mutant provide an explanation: a second, previously unobserved binding pocket allows medium-to-long acyl chains (≥ C8) to bind with an alternate conformation. Molecular simulations suggest that this pocket is more stable in FabB than in FabF, where mutations reduce the catalytic competency of longer chains instead of shifting them to the alternate pocket. Our findings indicate that homologous KSs differ not only in their primary binding sites but also in the availability of alternative binding modes that can buffer against mutational effects and enable functional diversification.

  PublisherOA PDFDOI

• Microplastic pollution induces algae blooms in experimental ponds but bioplastics are less harmful

  Communications Sustainability · 2026-01-19

  articleOpen access

  An ever-growing sea of plastic waste permeates even the most remote ecosystems; however, its ecological impact is unclear. Less persistent bioplastic alternatives are available but also have unknown environmental effects. We conducted a three-month experiment exposing plankton in experimental ponds to 10 concentrations of three different thermoplastic polyurethane microplastics, including two biodegradable bioplastics. Algal blooms with dense chlorophyll occurred consistently at high concentrations of the petroleum-derived thermoplastic polyurethane, but only occasionally with the two bioplastics. Herbivorous zooplankton density was strongly reduced by typical thermoplastic polyurethane and only weakly by bioplastics, therefore the effect on algae is at least partly due to reductions in top-down grazing pressure. Microbial communities exhibited compositional shifts in response to all three plastic types, with petroleum-derived plastic associated with the most pronounced differences across both prokaryotic and eukaryotic domains. Our results show that plastic pollution may contribute to the growing global problems of eutrophication, coastal hypoxia and harmful algae blooms, and that biodegradable plastics may have smaller environmental footprints.

  PublisherOA PDFDOI

• Exploring allomelanin: A comparative analysis via natural product extraction and synthesis

  Science Advances · 2026-02-13

  articleOpen access

  Allomelanin is a nitrogen-free class of melanin commonly found in plants and fungi. Although synthetic analogs have been developed from 1,8-dihydroxynaphthalene (1,8-DHN), detailed physicochemical comparisons with natural allomelanins remain limited. Herein, we extracted allomelanin from black knot fungus, chaga mushroom, and black oat using an acid-base extraction protocol, comparing them against a library of synthetic analogs derived from a range of putative, natural precursors. Spectroscopic analyses indicate that simple homopolymerization of 1,8-DHN does not adequately represent natural allomelanin structures. Instead, heterogeneous copolymerization of 1,8-DHN with catechol or tannic acid yields materials with physicochemical properties more consistent with natural extracts. This is also supported by their enhanced antioxidant and dye/metal adsorption properties. Like their synthetic counterparts, extracted natural allomelanins exhibit intrinsic porosity, reaching a Brunauer-Emmet-Teller area of 155 square meters per gram, potentially facilitating nutrient transport and toxin adsorption, although further studies will be required to probe this.

  PublisherDOI

• Comparative Genomics and Metabolomics of Domesticated, Pladienolide-Producing <i>Streptomyces</i> Bacteria

  Journal of Natural Products · 2026-03-10

  article

  Laboratory domestication of bacteria can negatively affect natural product production. This problem continues to plague discovery and development efforts. In this study, we investigated pladienolides from Streptomyces platensis, synthetic derivatives of which entered clinical trials for the treatment of acute myeloid leukemia. Solid cultures of the deposited S. platensis Mer-11107 yielded black, gray, and white colonies with identical 16S rRNA gene sequences, revealing that they were the same species. Importantly, metabolite analysis identified one white isolate with a 3-fold improvement in pladienolide B titers. Experimental evolution of black isolates gave rise to both gray and white colonies. In contrast, gray and white isolates did not generate the black phenotype, suggesting black isolates are ancestral strains and that the mechanism underlying the phenotypic heterogeneity is irreversible. Comparative genomics revealed sequence and structure variations that may help explain the observed differences in development and metabolite production. The increase in pladienolide titers with the white isolate is in line with the recent concept of division of labor within Streptomyces colonies, where genomic instability results in some cells specializing in antibiotic production and others remaining reproductive. Ultimately, identification of the pladienolide B overproducer will facilitate future studies in this important class of splice-modulating antitumor agents.

  PublisherDOI

• Abstract 7105: Therapeutic targeting of ADAR1 p150 splicing activity impairs CD44+ TNBC cell populations in preclinical studies

  Cancer Research · 2026-04-03

  article

  Abstract Background: Triple-negative breast cancer (TNBC) remains clinically challenging due to the lack of targeted therapies and the presence of therapy-resistant tumor-propagating cells. CD44 and ADAR1 contribute to TNBC progression and therapeutic resistance. Rebecsinib is a small-molecule inhibitor designed to block splicing-mediated activation of ADAR1 (adenosine deaminase acting on RNA 1). This study evaluates its efficacy in selectively targeting CD44+ and ADAR1+ cells in preclinical humanized TNBC models. Methods: MDA-MB-231 TNBC cell line-derived xenograft (CDX) models were established in Rag2-/-γc-/- and NSG-SGM3 mice. MDA-MB-231 ADAR-nanoluciferase-GFP expressing cells enable tracking of ADAR1 activity by IVIS imaging. Engrafted mice received vehicle, Rebecsinib IV (10 mg/kg), or Rebecsinib PO (15mg/kg), twice a week for two weeks. Tumor burden was measured by IVIS and single-cell suspensions from peripheral blood, and tissues (lung, liver, spleen, and bone marrow) were analyzed by flow cytometry to quantify CD44+ and ADAR1+ cells. Results: Rebecsinib significantly reduced CD44+ cells in peripheral blood (p &amp;lt; 0.05), lung (p &amp;lt; 0.01), liver (p &amp;lt; 0.01), and spleen (p &amp;lt; 0.05) in Rag2-/-γc-/- models (Student t test). Corresponding decreases in ADAR1+ cells was observed in the lung (p &amp;lt; 0.05), liver (p &amp;lt; 0.01), and spleen (p &amp;lt; 0.01) in NSG-SGM3 mouse models (Student t test). IVIS imaging demonstrated tumor bioluminescence in Rebecsinib-treated groups (p = 0.02, student t test). Combination with Fedratinib further suppressed tumor growth, indicating a synergistic effect (p &amp;lt; 0.05, student t test). Conclusion: Rebecsinib selectively reduces CD44+ and ADAR1+ TNBC cell populations and inhibits tumor progression in humanized preclinical models. These findings support further evaluation of Rebecsinib alone and in combination, as a targeted therapeutic approach for TNBC. Citation Format: Wenxue Ma, Jessica Pham, Emma Klacking, Kendale Wirtjes, Inge van der Werf, Peggy Wentworth, Sheldon Morris, James La Clair, Michael Burkart, Catriona Jamieson. Therapeutic targeting of ADAR1 p150 splicing activity impairs CD44+ TNBC cell populations in preclinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7105.

  PublisherDOI

• Abstract 7631: Predicting and preventing cancer stemness in low Earth orbit

  Cancer Research · 2026-04-03

  article

  Abstract Cancer stemness properties, including enhanced survival, malignant regeneration, telomere deregulation, genomic and epitranscriptomic instability, fuel metastases, and have been linked to stress, retrotransposon and inflammatory cytokine activation, which can occur in low earth orbit (LEO). In NASA Axiom 1, 2 and 3 missions to the ISS, confocal imaging, WGS, RNA-seq and scRNA-seq of lentiviral FUCCI2BL cell cycle and ADAR1-GFP reporter transduced erythroleukemia (TF-1a), colorectal (Caco-2) and metastatic breast cancer (MBC; MDA-MB-231 and patient samples) revealed proliferation, significant genomic instability, HERV and LINE-1 retrotransposon deregulation, and APOBEC3C and ADAR1 activation. Moreover, in Axiom 2 and 3 missions with ADAR1-reporter expressing MBC organoids and in humanized MBC mouse models, an ADAR1p150 splicing modulator, rebecsinib (IND 153126), prevented tumor propagation. Thus, cancer studies in LEO may accelerate the development of innovative cancer therapeutics and countermeasures for long-term spaceflight. Citation Format: Jessica Pham, Wenxue Ma, Claire Engstrom, Patrick Chang, Shuvro P. Nandi, Inge van der Werf, Emma Klacking, Teresa Sposito, Kendale Wirtjes, Thomas Frias, Antonio Ruiz, Jane Isquith, Luisa Ladel, Christina N. Wu, Jana Stoudemire, Pinar Mesci, Kay T. Yeung, Rebecca A. Shatsky, Anna A. Khachatrian, James J. La Clair, Michael D. Burkart, Peggy Wentworth, Curtis L. Scribner, Sheldon R. Morris, Thomas Whisenant, Karla Mack, Ludmil B. Alexandrov, Catriona H. Jamieson. Predicting and preventing cancer stemness in low Earth orbit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7631.

  PublisherDOI

• Advancing Renewable Materials via Microalgae-Derived Thermoplastic Polyester Polyurethanes

  ACS Sustainable Chemistry & Engineering · 2025-12-05 · 2 citations

  articleSenior authorCorresponding

  To remediate the growing global impacts of plastic waste, it is imperative to design sustainable materials that can be used as replacements for current nonrenewable and nonbiodegradable commercial products. Addressing this issue requires careful selection of both material class and renewable feedstock source to maximize the sustainability of production processes and end-of-life outcomes. This work describes the use of microalgae as a renewable feedstock for preparation of thermoplastic polyester polyurethane (TPU) materials. The sustainable and robust photosynthetic capacity of microalgae paired with cleavable bonds within the polyester TPU backbone result in a material that promotes efficient resource use and reduced ecological impact at the end of its life cycle. High-purity TPU monomers derived from Nannochloropsis salina oil were used to synthesize the first 100% microalgae-sourced TPU material from azelaic acid (AzA), 1,7-heptamethylene diisocyanate (7-HDI), and 1,9-nonanediol (NDO). For comparison, a TPU containing 75% microalgae-content was also prepared utilizing industry-standard 1,3-propanediol (PDO). Thermal and mechanical characterization was used to analyze the structure–function properties of the TPUs and assess potential industrial applications. Overall, this work seeks to offer a viable alternative to conventional plastics, supporting the global transition toward sustainable plastic usage.

  PublisherDOI

• Systematic Development of a Plasmon Ruler Using Dithiolate-Grafted Gold Nanoparticle for High-Throughput Screening of Anti-Icing Activity

  ACS Applied Nano Materials · 2025-03-24 · 3 citations

  article

  Here, we performed a systematic development of an assay based on a gold nanoparticle (AuNP) plasmon ruler to detect the activity of anti-icing reagents with superior stability and consistency in different phases (e.g., solid and liquid) applicable for standardized high-throughput screening (HTS). We found that dithiolate-grafted AuNPs indeed act as plasmon molecular rulers to measure the AuNPs interparticle distance during freezing. The plasmon ruler reflects the changes in ice crystallization in the presence of anti-icing reagents and can be used for standardized HTS of anti-icing reagents. We found that dithiolate ligands on the AuNP surface play a critical role in the assay performance. Molecular dynamics simulations showed that the anti-icing effects of the AuNPs are mostly sensitive to the ligand size and charges during cooling. Our optimized AuNP probe demonstrated higher colloidal stability and superior buffer resilience than previous versions, making it suitable for various types of target molecules, including chemicals, proteins, and organometals, with a high dynamic range of sensing. We investigated how the localized surface plasmon resonance peak or absorption spectrum correlates to ice formation and how this correlation can be used to evaluate the reagents’ anti-icing efficacy. We deconvoluted the measured spectra with theoretically derived unit spectra of a quantized AuNP cluster using COMSOL Multiphysics to calculate an apparent interparticle distance of AuNPs during ice formation and its changes in the presence of anti-icing reagents. We also proposed quantifying a AuNP-based colorimetric assay using dose–response Hill’s equation and an IC50 calculation, which is essential for a standardized HTS for anti-icing efficacy measurement. Then, we compared AuNP results with established assays, ice recrystallization inhibition, and dynamic ice, of which the dynamic changes of size and shape over time were analyzed using machine learning.

  PublisherDOI

• Identification and Overexpression of Endogenous Transcription Factors to Enhance Lipid Accumulation in the Commercially Relevant Species <i>Chlamydomonas pacifica</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-07

  preprintOpen access

  Abstract Sustainable low-carbon energy solutions are critical to mitigating global carbon emissions. Algae-based platforms offer potential by converting carbon dioxide into valuable products while aiding carbon sequestration. However, scaling algae cultivation faces challenges like contamination in outdoor systems. Previously, our lab evolved Chlamydomonas pacifica , an extremophile green alga, which tolerates high temperature, pH, salinity, and light, making it ideal for large-scale bioproduct production, including biodiesel. Here, we enhanced lipid accumulation in evolved C. pacifica by identifying and overexpressing key endogenous transcription factors through genome-wide in-silico analysis and in-vivo testing. These factors include Lipid Remodeling Regulator 1 (CpaLRL1), Nitrogen Response Regulator 1 (CpaNRR1), Compromised Hydrolysis of Triacylglycerols 7 (CpaCHT7), and Phosphorus Starvation Response 1 (CpaPSR1). Under nitrogen deprivation, CpaLRL1, CpaNRR1, and CpaCHT7 overexpression enhanced lipid accumulation compared to wildtype. However, CpaPSR1 increased lipid accumulation compared to wildtype in normal media despite causing no effect under nitrogen depravation, highlighting the difference in function based on media conditions. Notably, lipid analysis of CpaPSR1 under normal media conditions revealed a 2.4-fold increase in triglycerides (TAGs) compared to the wild type, highlighting its potential for biodiesel production. This approach provides a framework for transcription factor-focused metabolic engineering in algae, advancing bioenergy and biomaterial production. Graphical Abstract Created with BioRender.com .

  PublisherOA PDFDOI

• Tyrocidine synthetase modules 1 and 2 crosslinked in the condensation state, complex B

  EMPIAR dataset · 2025-09-02

  datasetOpen accessSenior author

  EMPIAR, the Electron Microscopy Public Image Archive centered at EMBL-EBI, is a public resource for raw electron microscopy images related to EMDB, contains micrographs, particle sets and tilt-series.

  PublisherDOI

Recent grants

• NIH Grant T32GM112584

  NIH · $729k · 2020

• NIH Grant R01GM086225

  NIH · $2.4M · 2012

• Enabling synthetic biology through single cell functional genomics

  NIH · $2.2M · 2022–2027

• NIH Grant R01GM094924

  NIH · $1.2M · 2015

• NIH Grant R03MH083266

  NIH · $25k · 2009

Frequent coauthors

• James J. La Clair

  Xenobe Research Institute

  135 shared

• Joseph P. Noel

  Salk Institute for Biological Studies

  58 shared

• Timothy L. Foley

  43 shared

• Arnold L. Rheingold

  University of California, San Diego

  38 shared

• Tony D. Davis

  University of California, San Diego

  32 shared

• Antonio G. DiPasquale

  29 shared

• Jeffrey T. Mindrebo

  Scripps Research Institute

  26 shared

• Martin J. Lear

  University of Lincoln

  26 shared

Labs

• Burkart LaboratoryPI

  The Burkart Laboratory focuses on characterizing carrier protein interactions in glycoside natural products, type I polyketide synthases, protein-protein interactions in Mycobacterium tuberculosis fatty acid biosynthesis, protein-protein interactions in type II fatty acid biosynthesis, fluorescent probe development for the discovery of novel polyketide synthase and non-ribosomal peptide synthase gene clusters, developing heterobifunctional small molecules (PROTACs) for applications in targeted protein degradation as well as the elucidation of biosynthetic pathways for natural products, the synthesis of natural product-based anti-cancer drug targets, and the expression of enzymes that further functionalize these drug targets, the investigation of protein-protein interaction in Sphingolipid biosynthesis pathway, cultivation of algae and synthesis of new monomers for the development of sustainable polymers, engineering novel hybrid polyketide synthase/non-ribosomal peptide synthase gene clusters using bioinformatics and structural biology, using structural biology to study biosynthesis in polyketide synthases, and using flow chemistry for the synthesis and characterization of organometallic materials, and studying bio-based sustainable plastics and flame retardant materials.

Education

• B.A.

  Rice University

• Ph.D., Organic Chemistry

  The Scripps Research Institute

Awards & honors

• NSF CAREER Award
• Sloan Research Fellowship
• Fellow of the American Association for the Advancement of Sc…
• Fellow of the Royal Society of Chemistry
• UC San Diego Chancellor’s Award for Excellence in Postdoctor…