Joseph M Bollinger
Pennsylvania State University, PA·Biochemistry
Some of the hardest chemical reactions, such as breaking strong carbon–hydrogen (C–H) bonds in otherwise inert molecules, are carried out with ease by enzymes that contain metal ions. These metalloenzymes use oxygen or peroxide at an iron or manganese center to make highly reactive radicals and then steer them toward one specific product.
- Fields
Biochemistry
Chemistry
Biophysics
- Topics
metalloenzymes
C–H activation
oxygen activation
- Grants
- 1 known grant, through Mar 2031
What they work on
- Determine how iron(II) and 2-oxoglutarate-dependent (Fe/2OG) oxygenases direct a common oxoiron(IV) intermediate toward hydroxylation, halogenation, desaturation, or cyclization, and test this by rationally redirecting reaction outcomes.
- Explain how heme-oxygenase-like diiron enzymes (HDOs) couple diiron cluster assembly with protein shape changes to form peroxodiiron(III) intermediates that cleave strong X–H bonds, and attempt to redirect their reactions.
- Uncover how class I ribonucleotide reductases (RNRs), enzymes that make DNA precursors, use diiron, manganese/iron, dimanganese, or flavin cofactors for the same C–H cleavage, and try to alter cofactor usage.
- Combine biochemical, biophysical, and computational methods to trace how cofactor use and reaction diversity evolved within these privileged protein architectures, informing directed evolution of new-to-nature reactivities.
More about the research
They are found in all three domains of life, and synthetic chemists both admire and try to copy them. A striking pattern is that the same protein framework can produce very different reactions from nearly identical metal cofactors (non-protein helpers), while structurally different cofactors can produce the same reaction. The program asks how protein scaffolds control these outcomes and how they evolved.
Why it matters
Engineered enzymes are increasingly used to make drugs, and these metalloenzymes perform C–H activation reactions that synthetic chemists often find difficult or impossible. Explaining how they control their outcomes could help chemists develop their shared protein scaffolds into biocatalysts for drug synthesis. It could also suggest strategies for inhibiting these enzymes therapeutically.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xiongyi Huang
Johns Hopkins University, MD·Chemistry
Engineer metalloenzymes — proteins with a catalytic metal center — to perform C–H functionalization reactions absent from natural biology, installing chemical groups of biomedical relevance into organic substrates.
Stephen Wiley Ragsdale
University of Michigan, MI·Biochemistry
Determine how the heme oxygenase-2 (HO2) catalytic core coordinates heme sequestration with its own lysosomal breakdown during heme deficiency, and test whether inducible HO1 also sequesters heme.
Rupal Gupta
College of Staten Island CUNY, NY·Biochemistry
Determine how 3-His iron-binding sites, an unusual alternative to the common 2-His-1-carboxylate motif, change the reaction mechanisms of non-heme iron enzymes that cut aromatic rings, using biochemical and spectroscopic methods.
The school
Pennsylvania State University: 60 labs on PI Pages, $1.3B a year on research, 743 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.