About

Alison Butler is a Distinguished Professor and Department Chair in the Department of Chemistry & Biochemistry at the University of California, Santa Barbara. Her specialization includes inorganic and organometallic biochemistry and biophysics, with a focus on biomedical sciences, biology-inspired chemistry and physics, organic and bioorganic chemistry. She received her Ph.D. from the University of California, San Diego in 1982, following her undergraduate studies at Reed College. Her postdoctoral work included positions at UCLA with Joan S. Valentine and at Caltech with Harry B. Gray. Dr. Butler's research interests are centered on bioinorganic chemistry, metallobiochemistry, and chemical biology, particularly in elucidating the roles of metal ions in the catalytic activities of metalloenzymes and understanding how microbes acquire transition metals for growth. Her research is primarily directed towards discovering new siderophores and investigating their biosynthetic pathways using genomics and bioinformatics, exploring adhesive properties of catechol siderophores, and studying oxidative disassembly of lignin employing metalloproteins and biomimetic metal complexes. Throughout her career, she has received numerous awards and honors, including election to the US National Academy of Sciences in 2022, fellowships in the American Association for the Advancement of Science, the American Chemical Society, and the Royal Society of Chemistry, as well as prestigious awards such as the ACS Alfred Bader Award, Cope Scholar Award, William H. Nichols Medal, and Richard C. Tolman Medal.

Research topics

• Biochemistry
• Chemistry
• Combinatorial chemistry
• Organic chemistry
• Biology
• Stereochemistry
• Nanotechnology
• Evolutionary biology
• Materials science
• Microbiology

Selected publications

• Author response: Automated genome mining predicts structural diversity and taxonomic distribution of peptide metallophores across bacteria

  2026-03-09

  peer-reviewOpen access
  PublisherDOI

• Nature's diazeniumdiolates: Metal coordination and reactivity

  Polyhedron · 2026-02-13

  articleSenior authorCorresponding
  PublisherDOI

• Automated genome mining predicts structural diversity and taxonomic distribution of peptide metallophores across bacteria

  eLife · 2026-03-09

  articleOpen access

  Microbial competition for trace metals shapes their communities and interactions with humans and plants. Many bacteria scavenge trace metals with metallophores, small molecules that chelate environmental metal ions. Metallophore production may be predicted by genome mining, where genomes are scanned for homologs of known biosynthetic gene clusters (BGCs). However, accurately detecting non-ribosomal peptide (NRP) metallophore biosynthesis requires expert manual inspection, stymieing large-scale investigations. Here, we introduce automated identification of NRP metallophore BGCs through a comprehensive algorithm, implemented in antiSMASH, that detects chelator biosynthesis genes with 97% precision and 78% recall against manual curation. We showcase the utility of the detection algorithm by experimentally characterizing metallophores from several taxa. High-throughput NRP metallophore BGC detection enabled metallophore detection across 69,929 genomes spanning the bacterial kingdom. We predict that 25% of all bacterial non-ribosomal peptide synthetases encode metallophore production and that significant chemical diversity remains undiscovered. A reconstructed evolutionary history of NRP metallophores supports that some chelating groups may predate the Great Oxygenation Event. The inclusion of NRP metallophore detection in antiSMASH will aid non-expert researchers and continue to facilitate large-scale investigations into metallophore biology.

  PublisherDOI

• Automated genome mining predicts structural diversity and taxonomic distribution of peptide metallophores across bacteria

  eLife · 2026-02-03

  articleOpen access

  Microbial competition for trace metals shapes their communities and interactions with humans and plants. Many bacteria scavenge trace metals with metallophores, small molecules that chelate environmental metal ions. Metallophore production may be predicted by genome mining, where genomes are scanned for homologs of known biosynthetic gene clusters (BGCs). However, accurately detecting non-ribosomal peptide (NRP) metallophore biosynthesis requires expert manual inspection, stymieing large-scale investigations. Here, we introduce automated identification of NRP metallophore BGCs through a comprehensive algorithm, implemented in antiSMASH, that detects chelator biosynthesis genes with 97% precision and 78% recall against manual curation. We showcase the utility of the detection algorithm by experimentally characterizing metallophores from several taxa. High-throughput NRP metallophore BGC detection enabled metallophore detection across 69,929 genomes spanning the bacterial kingdom. We predict that 25% of all bacterial non-ribosomal peptide synthetases encode metallophore production and that significant chemical diversity remains undiscovered. A reconstructed evolutionary history of NRP metallophores supports that some chelating groups may predate the Great Oxygenation Event. The inclusion of NRP metallophore detection in antiSMASH will aid non-expert researchers and continue to facilitate large-scale investigations into metallophore biology.

  PublisherDOI

• Periplasmic Binding Protein YiuA Enables <i>Yersinia pestis</i> to Scavenge Fe(III)-Catechol Siderophores

  ACS Infectious Diseases · 2025-08-14

  articleOpen accessSenior authorCorresponding

  Yersinia pestis, the pathogen causing plague, requires iron to grow. Y. pestis employs several uptake pathways for iron, including the siderophore yersiniabactin, as well as hemin and inorganic iron. The Y. pestis iron assimilation repertoire further harbors the uncharacterized YiuRABC pathway, presumed to transport an unidentified Fe(III)-siderophore(s). Through intrinsic fluorescence quenching of the periplasmic binding protein YiuA, we discovered that YiuA displays high affinity toward Fe(III) complexes of the hydrolysis products of enterobactin, Fe(III)-[di(DHB-LSer)] and Fe(III)-[DHB-LSer]2, with Kd values of 27.6 ± 4.2 nM and 28.2 ± 6.9 nM, respectively, as well as the bis-catechol siderophore butanochelin, with Kd 0.76 ± 0.17 nM. By comparison, YiuA has a much weaker affinity for intact Fe(III)-enterobactin, Kd 444.7 ± 20.6 nM. Electronic circular dichroism spectroscopy reveals YiuA has a strong preference for binding Λ configured Fe(III)-siderophores, which can be achieved with the Fe(III) bis-catechol complexes but not Fe(III)-enterobactin.

  PublisherOA PDFDOI

• Coordination Chemistry of an Emerging Group of Diazeniumdiolate Siderophores: Crystal Structures of M(III)-Gramibactin (M= Fe and Ga)

  Journal of the American Chemical Society · 2025-09-19 · 2 citations

  articleOpen accessSenior authorCorresponding

  -diazeniumdiolate as a new Fe(III)-binding group in siderophores. Gramibactin is a mixed ligand siderophore, comprised of two graminine residues harboring the diazeniumdiolate donors and a β-hydroxy-aspartate donor. Diazeniumdiolate siderophores have so far evaded crystallographic characterization and few structures of synthetic diazeniumdiolate complexes are reported. To address the gap in structural information, the complexes K[M(III)-gramibactin] (M = Fe and Ga) were prepared, crystallized and their structures solved by X-ray diffraction (XRD). The four Fe-O bond lengths in the two diazeniumdiolates are quite similar, ranging from 1.978 Å to 2.059 Å, indicating an equal contribution in bonding. In contrast, the differing Fe-O bond lengths in β-hydroxy-aspartate reflect the relative donor strengths of the carboxylate (1.997 Å) and alkoxide (1.902 Å) groups. Gramibactin coordinates Fe(III) in a Δ-configured distorted octahedral geometry. The diamagnetic nature of Ga(III) is often leveraged in NMR studies to infer the solution structure of the corresponding Fe(III)-siderophores, which are assumed to be identical. The structural similarity of Ga(III)- and Fe(III)-gramibactin is striking and represents the first crystallographic verification of the assumed isostructural relationship between a Ga(III)- and an Fe(III)-siderophore. By providing concrete evidence, this study promotes Ga(III) as a reliable proxy for Fe(III) in siderophore complexes, with implications for solution structure determination of siderophores and design of Ga(III)-siderophore-based theranostics.

  PublisherOA PDFDOI

• Substrate flexibility of the catechol siderophore periplasmic binding proteins, RupB and YiuA from Yersinia ruckeri YRB

  Journal of Inorganic Biochemistry · 2025-11-19

  articleSenior authorCorresponding
  PublisherDOI

• In memoriam: Carl J. Carrano

  BioMetals · 2025-03-12 · 1 citations

  reviewOpen access

  This article is a celebration of the life and work of Carl J. Carrano who, from a childhood in Long Island, New York, built a career in bioinorganic chemistry, especially in the context of metal uptake and halogen metabolism in microbes and marine organisms.

  PublisherOA PDFDOI

• Automated genome mining predicts structural diversity and taxonomic distribution of peptide metallophores across bacteria

  eLife · 2025-10-30

  articleOpen access

  Microbial competition for trace metals shapes their communities and interactions with humans and plants. Many bacteria scavenge trace metals with metallophores, small molecules that chelate environmental metal ions. Metallophore production may be predicted by genome mining, where genomes are scanned for homologs of known biosynthetic gene clusters (BGCs). However, accurately detecting non-ribosomal peptide (NRP) metallophore biosynthesis requires expert manual inspection, stymieing large-scale investigations. Here, we introduce automated identification of NRP metallophore BGCs through a comprehensive algorithm, implemented in antiSMASH, that detects chelator biosynthesis genes with 97% precision and 78% recall against manual curation. We showcase the utility of the detection algorithm by experimentally characterizing metallophores from several taxa. High-throughput NRP metallophore BGC detection enabled metallophore detection across 69,929 genomes spanning the bacterial kingdom. We predict that 25% of all bacterial non-ribosomal peptide synthetases encode metallophore production and that significant chemical diversity remains undiscovered. A reconstructed evolutionary history of NRP metallophores supports that some chelating groups may predate the Great Oxygenation Event. The inclusion of NRP metallophore detection in antiSMASH will aid non-expert researchers and continue to facilitate large-scale investigations into metallophore biology.

  PublisherDOI

• Stereospecific control of microbial growth by a combinatoric suite of chiral siderophores

  Proceedings of the National Academy of Sciences · 2025-03-03 · 2 citations

  articleOpen accessSenior authorCorresponding

  Bacteria compete for iron by producing small-molecule chelators known as siderophores. The triscatechol siderophores trivanchrobactin and ruckerbactin, produced by Vibrio campbellii DS40M4 and Yersinia ruckeri YRB, respectively, are naturally occurring diastereomers that form chiral ferric complexes in opposing enantiomeric configurations. Chiral recognition is a hallmark of specificity in biological systems, yet the biological consequences of chiral coordination compounds are relatively unexplored. We demonstrate stereoselective discrimination of microbial growth and iron uptake by chiral Fe(III)–siderophores. The siderophore utilization pathway in V. campbellii DS40M4 is stereoselective for Λ-Fe(III)–trivanchrobactin, but not the mismatched Δ-Fe(III)–ruckerbactin diastereomer. Chiral recognition is likely conferred by the stereospecificity of both the outer membrane receptor (OMR) protein FvtA and the periplasmic binding protein (PBP) FvtB, both of which must interact preferentially with the Λ-configured Fe(III)-coordination complexes.

  PublisherDOI

Recent grants

• Bioinorganic Chemistry of Catechols: Siderophores, Adhesive Proteins and Biomimetic Analogs

  NSF · $480k · 2017–2021

• Biomimetic and Enzyme Investigations of Haloperoxides

  NSF · $330k · 1996–2001

• Bioinorganic Chemistry of Catechol-Amine Siderophores and Biomimetic Analogs: Chirality of Iron Coordination and Bacterial Uptake

  NSF · $881k · 2021–2026

• Mechanistic Investigations of Vanadium Haloperoxidases

  NSF · $455k · 2007–2012

• NIH Grant R55GM038130

  NIH · $100k · 1994

Frequent coauthors

• Shigenobu Yano

  Nara Women's University

  81 shared

• Yoshihito Watanabe

  Nagoya University

  81 shared

• John Groves

  81 shared

• Kenneth D. Karlin

  Johns Hopkins University

  81 shared

• John H. Dawson

  81 shared

• Ann M. English

  PROTEO

  81 shared

• Michael T. Murray

  University of Sydney

  34 shared

• Moriah Sandy

  University of California, San Francisco

  30 shared

Education

• PhD in Chemistry, Department of Chemistry & Biochemistry

  University of California San Diego

  1982

• BAS in Chemistry, Chemistry

  Reed College

  1977

Awards & honors

• American Cancer Society Junior Faculty Research Award
• Fellow of the American Association for the Advancement of Sc…
• Fellow of the American Chemical Society (2012)
• Fellow of the Royal Society of Chemistry (2019)
• Fellow of the American Academy of Arts and Sciences (2019)