About

Peter Leslie Dutton is an Emeritus Professor of Biochemistry and Biophysics at the University of Pennsylvania's Perelman School of Medicine. His educational background includes a B.Sc. in Chemistry (Honors) and a Ph.D. in Biochemistry from the University of Wales. His research focuses on understanding the factors governing electron tunneling through natural proteins involved in electron transfer, energy conversion, signaling, regulation, and enzyme redox catalysis. He is also engaged in the de novo design and synthesis of proteins engineered to perform natural functions such as electron transfer, proton translocation, charge-driven conformational changes, and redox catalysis in highly simplified, structured settings.

Research topics

• Chemistry
• Photochemistry
• Stereochemistry
• Crystallography
• Biochemistry

Selected publications

• Artificial oxygen transport protein

  OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) · 2023-01-23

  articleOpen access1st authorCorresponding

  This invention provides heme-containing peptides capable of binding molecular oxygen at room temperature. These compounds may be useful in the absorption of molecular oxygen from molecular oxygen-containing atmospheres. Also included in the invention are methods for treating an oxygen transport deficiency in a mammal.

  PublisherOA PDF

• Tailorable Tetrahelical Bundles as a Toolkit for Redox Studies

  The Journal of Physical Chemistry B · 2022-10-11 · 5 citations

  articleOpen accessSenior author

  values of bound cofactors.

  PublisherOA PDFDOI

• The aprotic electrochemistry of quinones

  Biochimica et Biophysica Acta (BBA) - Bioenergetics · 2022-04-09 · 41 citations

  article
  PublisherDOI

• De novo protein design of photochemical reaction centers

  Nature Communications · 2022-08-23 · 35 citations

  articleOpen access

  Natural photosynthetic protein complexes capture sunlight to power the energetic catalysis that supports life on Earth. Yet these natural protein structures carry an evolutionary legacy of complexity and fragility that encumbers protein reengineering efforts and obfuscates the underlying design rules for light-driven charge separation. De novo development of a simplified photosynthetic reaction center protein can clarify practical engineering principles needed to build new enzymes for efficient solar-to-fuel energy conversion. Here, we report the rational design, X-ray crystal structure, and electron transfer activity of a multi-cofactor protein that incorporates essential elements of photosynthetic reaction centers. This highly stable, modular artificial protein framework can be reconstituted in vitro with interchangeable redox centers for nanometer-scale photochemical charge separation. Transient absorption spectroscopy demonstrates Photosystem II-like tyrosine and metal cluster oxidation, and we measure charge separation lifetimes exceeding 100 ms, ideal for light-activated catalysis. This de novo-designed reaction center builds upon engineering guidelines established for charge separation in earlier synthetic photochemical triads and modified natural proteins, and it shows how synthetic biology may lead to a new generation of genetically encoded, light-powered catalysts for solar fuel production.

  PublisherOA PDFDOI

• Rational design of photosynthetic reaction center protein maquettes

  Frontiers in Molecular Biosciences · 2022-09-21 · 20 citations

  articleOpen access

  New technologies for efficient solar-to-fuel energy conversion will help facilitate a global shift from dependence on fossil fuels to renewable energy. Nature uses photosynthetic reaction centers to convert photon energy into a cascade of electron-transfer reactions that eventually produce chemical fuel. The design of new reaction centers de novo deepens our understanding of photosynthetic charge separation and may one day allow production of biofuels with higher thermodynamic efficiency than natural photosystems. Recently, we described the multi-step electron-transfer activity of a designed reaction center maquette protein (the RC maquette), which can assemble metal ions, tyrosine, a Zn tetrapyrrole, and heme into an electron-transport chain. Here, we detail our modular strategy for rational protein design and show that the intended RC maquette design agrees with crystal structures in various states of assembly. A flexible, dynamic apo-state collapses by design into a more ordered holo-state upon cofactor binding. Crystal structures illustrate the structural transitions upon binding of different cofactors. Spectroscopic assays demonstrate that the RC maquette binds various electron donors, pigments, and electron acceptors with high affinity. We close with a critique of the present RC maquette design and use electron-tunneling theory to envision a path toward a designed RC with a substantially higher thermodynamic efficiency than natural photosystems.

  PublisherOA PDFDOI

• De Novo Protein Design of Photochemical Reaction Centers

  Research Square · 2021-11-18 · 3 citations

  preprintOpen access

  Abstract Natural photosynthetic protein complexes capture sunlight to power the energetic catalysis that supports life on Earth. Yet these natural protein structures carry an evolutionary legacy of complexity and fragility that encumbers protein reengineering efforts and obfuscates the underlying design rules for light-driven charge separation. De novo development of a simplified photosynthetic reaction center protein can clarify practical engineering principles needed to build new enzymes for efficient solar-to-fuel energy conversion. Here we report the rational design, X-ray crystal structure, and electron transfer activity of a multi-cofactor protein that incorporates essential elements of photosynthetic reaction centers. This highly stable, modular artificial protein framework can be reconstituted in vitro with interchangeable redox centers for nanometer-scale photochemical charge separation. Transient absorption spectroscopy demonstrates Photosystem II-like tyrosine and metal cluster oxidation, and we measure charge separation lifetimes exceeding 100 ms, ideal for light-activated catalysis. This de novo-designed reaction center builds upon engineering guidelines established for charge separation in earlier synthetic photochemical triads and modified natural proteins, and it shows how synthetic biology may lead to a new generation of genetically encoded, light-powered catalysts for solar fuel production.

  PublisherOA PDFDOI

• Emulating photosynthetic processes with light harvesting synthetic protein (maquette) assemblies on titanium dioxide

  Materials Advances · 2020-01-01 · 4 citations

  articleOpen access

  The first working artificial photosynthetic photoanode using a light harvesting maquette, a synthetic protein with a metalloporphyrin ligated to it, has been fabricated that generates remarkably high photocurrent for a protein-based device.

  PublisherOA PDFDOI

• A Thermostable Protein Matrix for Spectroscopic Analysis of Organic Semiconductors

  Journal of the American Chemical Society · 2020-07-16 · 4 citations

  articleOpen access

  Advances in protein design and engineering have yielded peptide assemblies with enhanced and non-native functionalities. Here, various molecular organic semiconductors (OSCs), with known excitonic up- and down-conversion properties, are attached to a de novo-designed protein, conferring entirely novel functions on the peptide scaffolds. The protein-OSC complexes form similarly sized, stable, water-soluble nanoparticles that are robust to cryogenic freezing and processing into the solid-state. The peptide matrix enables the formation of protein-OSC-trehalose glasses that fix the proteins in their folded states under oxygen-limited conditions. The encapsulation dramatically enhances the stability of protein-OSC complexes to photodamage, increasing the lifetime of the chromophores from several hours to more than 10 weeks under constant illumination. Comparison of the photophysical properties of astaxanthin aggregates in mixed-solvent systems and proteins shows that the peptide environment does not alter the underlying electronic processes of the incorporated materials, exemplified here by singlet exciton fission followed by separation into weakly bound, localized triplets. This adaptable protein-based approach lays the foundation for spectroscopic assessment of a broad range of molecular OSCs in aqueous solutions and the solid-state, circumventing the laborious procedure of identifying the experimental conditions necessary for aggregate generation or film formation. The non-native protein functions also raise the prospect of future biocompatible devices where peptide assemblies could complex with native and non-native systems to generate novel functional materials.

  PublisherOA PDFDOI

• Outline of theory of protein electron transfer

  Garland Science eBooks · 2020-07-24 · 7 citations

  book-chapterSenior author

  The chemiosmotic hypothesis describes the central feature of biological energy transduction as the creation of a transmembrane proton gradient from redox potential energy of photosynthesis and respiration. The gradient is built up by a series of guided electron transfers within and between membranous proteins that selectively move electrons and protons without compromising the insulation of the membrane. Small protein units have several thousands of atoms integrated into convoluted structures. Attempts to build a complete theoretical description of the behaviour of these systems are forced immediately into drastic simplifications. To relate the tunnelling theory to observation, we must be able to derive an electron transfer rate. However, in the simple quantum mechanical view, an electron will penetrate the barrier to the acceptor well but then return through the barrier back to the donor in a resonant process that depends on the distance between and the relative energy of the wells.

  PublisherDOI

• Ultrafast flavin/tryptophan radical pair kinetics in a magnetically sensitive artificial protein

  Physical Chemistry Chemical Physics · 2019-01-01 · 16 citations

  articleOpen access

  Radical pair formation and decay are implicated in a wide range of biological processes including avian magnetoreception. However, studying such biological radical pairs is complicated by both the complexity and relative fragility of natural systems. To resolve open questions about how natural flavin-amino acid radical pair systems are engineered, and to create new systems with novel properties, we developed a stable and highly adaptable de novo artificial protein system. These protein maquettes are designed with intentional simplicity and transparency to tolerate aggressive manipulations that are impractical or impossible in natural proteins. Here we characterize the ultrafast dynamics of a series of maquettes with differing electron-transfer distance between a covalently ligated flavin and a tryptophan in an environment free of other potential radical centers. We resolve the spectral signatures of the cysteine-ligated flavin singlet and triplet states and reveal the picosecond formation and recombination of singlet-born radical pairs. Magnetic field-sensitive triplet-born radical pair formation and recombination occurs at longer timescales. These results suggest that both triplet- and singlet-born radical pairs could be exploited as biological magnetic sensors.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R37GM027309

  NIH · $3.0M · 1999

• NIH Grant R01GM041048

  NIH · $7.4M · 2015

• NIH Grant R01GM027309

  NIH · $5.2M · 2013

• NIH Grant P01GM048130

  NIH · $17.8M · 2010

• NIH Grant T32GM008275

  NIH · $9.5M · 2019

Frequent coauthors

• Christopher C. Moser

  University of Pennsylvania

  489 shared

• Artur Osyczka

  Jagiellonian University

  142 shared

• Brian R. Gibney

  City University of New York

  142 shared

• Roger C. Prince

  111 shared

• Goutham Kodali

  92 shared

• Francesc Rabanal

  Universitat de Barcelona

  91 shared

• Dan E. Robertson

  85 shared

• A. Joshua Wand

  Texas A&M University

  67 shared

Education

• PhD, Biochemistry

  University of Wales

  1967

• BS, Chemistry

  University of Wales

  1963