About

Sean J. Elliott, Ph.D., is a Professor in the Chemistry Department at Boston University College of Engineering. He holds a Ph.D. in Bioinorganic Chemistry from Caltech, obtained in 2000. His research group, The Elliott Group, combines interests in catalysis sciences with metalloprotein structure-function relationships and enzymology. A specific emphasis of his group is the development of adsorbed electrochemistry and the use of electrocatalysis with spectroscopy to understand important transformations of environmental forms of nitrogen, carbon, oxygen, and sulfur. Dr. Elliott has been recognized with several honors, including the Scialog® Award from the Research Corporation in 2010 and 2011, the Gitner Award for Distinguished Teaching at Boston University in 2007, and the National Science Foundation CAREER Award in 2005. He was also a EMBO Postdoctoral Long-term Fellow at the University of Oxford from 2000 to 2001. His primary appointment is within the Chemistry Department, and he is affiliated with the Division of Materials Science and Engineering at Boston University.

Research topics

• Chemistry
• Biochemistry
• Stereochemistry
• Organic chemistry
• Crystallography
• Combinatorial chemistry
• Inorganic chemistry
• Mathematics

Selected publications

• Balancing redox-mediated cytotoxicity and catalysis in natural product biosynthesis

  ChemRxiv · 2026-03-26

  articleOpen access

  Redox-mediated chemistry is central to both the biosynthesis and cytotoxicity of many natural products, yet how microbes balance these processes remains poorly understood. Here, we uncover a conserved mechanism that coordinates three redox-mediated processes in secondary metabolite biosynthesis: self-protection, prevention of substrate degradation, and late-stage biocatalysis. Using the antitumor antibiotic doxorubicin as a model system, we show that the Vicinal Oxygen Chelate (VOC) protein DnrV prevents reactive oxygen species formation and substrate degradation while promoting P450 catalysis. We expand this paradigm to a conserved family of VOC-fold proteins, REdox-Associated CytoToxin binding proteins (REACT), found across bacteria, fungi, and plants. REACT represents a multifunctional protein class that balances antibiotic assembly, self-protection, and prevention of metabolite destruction, providing a foundational understanding of production of redox-active natural products.

  PublisherOA PDFDOI

• An Evolutionarily Conserved Protein Fold with Multiple Roles in Anthracycline Biosynthesis

  ChemRxiv · 2025-08-05

  preprintOpen access

  Doxorubicin, a glycosylated type II PKS-derived natural product first isolated from Streptomyces peucetius is a widely prescribed anticancer medicine and cytotoxic agent. It is also the final oxidation product of DoxA, a cytochrome P450 that catalyzes three sequential C–H oxidation reactions at the C13 and C14 positions on deoxy-daunorubicin leading to doxorubicin. A key limitation of in vitro P450 biocatalysis with anthracycline substrates is the rapid reductive de-glycosylation in the presence of electron donors like NADPH and ferredoxin reductase leading to inactive aglycones. This undesired reaction derails late-stage oxidative functionalization of anthracycline derivatives for clinical development. Recently, we demonstrated that DnrV, a previously uncharacterized vicinal oxygen chelate (VOC) protein in the doxorubicin BGC, prevents reductive activation thereby mitigating the cellular redox stress and metabolite destruction associated with redox cycling. In this study, we employed biochemical, biophysical, and structural methods to elucidate the molecular basis of DnrV function. Our analyses revealed that DnrV is a multifunctional protein that simultaneously modulates the redox characteristics of the bound anthracycline and induces catalytic rate enhancement of the iterative cytochrome P450 DoxA. These are novel functions of the ancient VOC protein family, representing a new functional class we term REdox-Associated CytoToxin binding protein (REACT). Homologues of DnrV from non-anthracycline BGCs display similar redox-protective activity, and some extend this function to the bacterial metabolite menadione. These findings establish REACTs as a conserved family of multifunctional proteins that modulate quinone redox behavior and promote oxidative tailoring of redox-active natural products.

  PublisherOA PDFDOI

• Electrocatalytic Nitrite Reduction by a Monomeric NrfA: Commonality in Ammonification Mechanisms

  Biochemistry · 2025-03-03 · 1 citations

  articleOpen accessSenior authorCorresponding

  Cytochrome c nitrite reductase (NrfA) is a pentaheme enzyme capable of the six-electron reduction of nitrite to ammonia, which is a key step in the nitrogen cycle. All NrfA enzymes appear to have a branched set of two heme-based pathways for electron transfer to a conserved active site, and until recently, NrfA enzymes from a variety of microorganisms were considered to possess a homodimeric structure; yet, recent efforts have shown that in solution, purified Geobacter lovleyi (Gl) NrfA is a monomer. Direct protein electrochemistry has been used in the past to characterize the dimeric NrfAs from Escherichia coli and Shewanella oneidensis, revealing features of maximal activity as a function of nitrite concentration, and redox poise, both of which were interpreted in terms of the dimeric structure providing multiple redox equivalents. Here, we examine Gl NrfA using protein film electrochemistry and find that all of the features that were associated with the dimeric enzymes are also found in the monomeric enzyme. Further, we probe the contribution of specific heme environments through investigation of two His to Met heme ligand mutants, each along a different branch of the electron transfer network, which demonstrates that each path is likely essential to support native-like catalysis.

  PublisherDOI

• The redox landscape of pyruvate:ferredoxin oxidoreductases reveals often conserved Fe–S cluster potentials

  Journal of Biological Chemistry · 2025-06-16 · 2 citations

  articleOpen accessSenior author

  Here, we investigate the thermodynamic driving force of internal electron transfer of pyruvate:ferredoxin oxidoreductases (PFORs), by comparing the redox properties of a series of PFORs from Chlorobaculum tepidum, Magnetococcus marinus, Methanosarcina acetivorans, as well as revisiting the single historical precedent, the enzyme from Desulfovibrio africanus. These enzymes require a thiamine pyrophosphate cofactor, three [4Fe-4S] clusters, and CoA for activity and are found within anaerobic organisms that utilize the reverse tricarboxylic acid cycle, or other reductive pathways, performing carbon dioxide reduction and pyruvate synthesis. Yet, PFOR is often invoked as an oxidative enzyme responsible for generating reducing equivalents in the form of the redox carrier ferredoxin. Previous efforts to understand the mechanism of PFOR have relied upon a prior report of the iron-sulfur redox potentials derived from an incomplete redox titration. Here, we use direct protein film electrochemistry to provide a side-by-comparison of four PFOR enzymes, providing a new assessment of the iron-sulfur cluster redox potentials. As the Methanosarcina acetivorans PFOR is comprised of multiple polypeptides, our investigation of the recombinant PorD subunit allows us to construct a model, where the revised redox potentials are mapped to specific iron-sulfur clusters.

  PublisherOA PDFDOI

• Author response for "Reactivity of canonical bacterial cytochrome c peroxidases: insights into the electronic structure of Compound I"

  2025-02-05

  peer-reviewSenior author
  PublisherDOI

• Reactivity of canonical bacterial cytochrome <i>c</i> peroxidases: insights into the electronic structure of compound I

  Chemical Science · 2025-01-01 · 5 citations

  articleOpen accessSenior authorCorresponding

  Bacterial cytochrome c peroxidase (bCcP) family members include di-heme enzymes that are capable of producing various high oxidation states in their reactions with the substrate H 2 O 2 .

  PublisherDOI

• <i>Escherichia coli</i> Triheme Enzyme YhjA: Structure and Reactivity

  Biochemistry · 2025-07-16 · 1 citations

  articleSenior authorCorresponding

  It has been recently realized that some Gram-negative organisms such as Escherichia coli produce a multiheme cytochrome c to serve as a quinol peroxidase that couples electrons from the quinol pool directly to H2O2. The E. coli version of this enzyme, termed YhjA, has been predicted to be a member of the bacterial cytochrome c peroxidase (bCCP) superfamily, where a novel N-terminal single-heme binding domain is fused to the canonical bCCP diheme domain found widely in Gram-negative bacteria. Here, we present an X-ray crystal structure of YhjA, revealing the triheme architecture that nature has employed to couple the quinol pool to the reduction of H2O2. We also show kinetic, spectroscopic, and electrochemical data that detail the differences between the three hemes that are observed in the structure, where two of the heme irons are both six-coordinate, ligated by Met and His residues, and the third peroxidatic heme is found to be five-coordinate. Electrocatalytic voltammetry of YhjA illustrates how the high-potential hemes serve as relays to the peroxidatic active site. Together, these data suggest a model of the catalytic chemistry of YhjA, illustrating how this member of the bCCP family may react with substrates and engage in multielectron redox reactions.

  PublisherDOI

• Abstract 2804 From Nitrite to Ammonia: The Role of Cytochrome c Nitrite Reductase (NrfA)

  Journal of Biological Chemistry · 2025-05-01

  articleOpen access

  Nitrate and nitrite are serious contaminants of waterways that can lead to eutrophication. Certain organisms, however, can convert nitrate and nitrite to ammonium via the dissimilatory nitrate reduction to ammonium (DNRA) pathway. One of the enzyme complexes capable of performing DNRA is comprised of two proteins: NrfH, a membrane-bound quinol oxidase, and its redox partner NrfA, a soluble periplasmic nitrite ammonifier. NrfA catalyzes the six-electron, eight-proton reduction of nitrite to ammonium and helps retain nitrogenous nutrients in the soil.

  PublisherOA PDFDOI

• Assessing the role of redox carriers in the reduction of CO2 by the oxo-acid: ferredoxin oxidoreductase superfamily

  Methods in enzymology on CD-ROM/Methods in enzymology · 2024-01-01 · 2 citations

  articleSenior authorCorresponding
  PublisherDOI

• Structural organization of pyruvate: ferredoxin oxidoreductase from the methanogenic archaeon Methanosarcina acetivorans

  Structure · 2024-09-11 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM072663

  NIH · $1.2M · 2012

• Connections between redox chemistry and catalysis in multiheme peroxidases

  NSF · $300k · 2013–2017

• Redox Reactions of the AdoMet Radical Enzyme Superfamily

  NIH · $1.3M · 2016–2021

• Structure, Function and Diversity in the Bacterial Cytochrome c Peroxidase Family

  NIH · $1.3M · 2017–2021

• CAREER: Bioinorganic Redox Chemistry and Protein-Protein Interactions at an Electrode

  NSF · $846k · 2006–2012

Frequent coauthors

• Catherine L. Drennan

  Massachusetts Institute of Technology

  42 shared

• Sunney I. Chan

  Institute of Chemistry, Academia Sinica

  19 shared

• Michael J. Hamill

  Flagship Pioneering (United States)

  16 shared

• Kara L. Bren

  University of Rochester

  15 shared

• Squire J. Booker

  Pennsylvania State University

  12 shared

• Hiep-Hoa T. Nguyen

  11 shared

• Kent H. Nakagawa

  Photometrics (United States)

  10 shared

• Héctor H. Hernández

  Khalifa University of Science and Technology

  10 shared

Education

• Ph.D. in Bioinorganic Chemistry, Chemistry and Chemical Engineering

  Caltech

  2000

• B.A. in Chemistry and English

  Amherst College

  1994

Awards & honors

• Scialog® Award, Research Corporation, 2010 and 2011
• Gitner Award for Distinguished Teaching, Boston University,…
• National Science Foundation CAREER Award, 2005
• EMBO Postdoctoral Long-term Postdoctoral Fellow at the Unive…