Assistant Professor
Biochemistry

B.A., Chemistry and French; 2017, Wabash College
Ph.D., Chemistry; 2022, University of Illinois Urbana-Champaign

Office: S-051G
Phone: (812) 237-2016
E-mail: Justin.Miller@indstate.edu
https://orcid.org/0000-0002-3529-6097

Research Summary

Cytochrome P450s (CYPs, P450s) are a superfamily of enzymes found across the biosphere—plants, animals, other eukaryotes, bacteria, archaea, and viruses. These iron-containing hemoproteins take electrons from a partner protein and protons from solution to activate molecular oxygen and directly oxidize small molecules. With P450s having roles in drug metabolism, hormone biosynthesis, and specialized metabolism (nature’s version of chemical warfare), the study of this diverse set of proteins has applications spanning pharmacology, agriculture, ecology, and biotechnology.
Dr. Miller’s particular research interests center in two areas:
1. Developing CYPs for Direct C-H Amination:
Although synthetic methods in chemistry are embracing more enzymatic transformations, biocatalytic methods for installing amine functional groups are largely limited transforming ketones to amines by reductive amination. This project seeks to adapt the ability of P450s to selectively activate C-H bonds with oxygen to selectively aminate C-H bonds using cheap nitrogen sources like azide and hydroxylamine. This work includes training in an array of techniques in bioinorganic chemistry—cloning, heterologous protein expression, protein purification, anaerobic protein assays, spectroscopy, computer modeling of protein structure, and conducting in vitro assays with gas chromatography and liquid chromatography assessment.
2. Discovering Targeted CYP Inhibitors as Selective Antibiotics in a Course-Based Undergraduate Research Experience (CURE):
The spread of antibiotic resistance amongst bacteria is a growing international threat to public health. One strategy for stymying the spread of antibiotic resistance is the development of species-selective antibiotics for common infections. Several bacterial P450s have been implicated in disease states from pathogens such as Mycobacterium tuberculosis and Pseudomonas aeruginosa. Using heterologous expression with non-pathogenic bacteria, protein purification methods, and an array of biochemical methods, students in the Biochemistry I Laboratory (CHEM 431L) course will investigate a disease-implicated P450, screen a library of small molecules as potential inhibitors, and evaluate the inhibitory abilities of positive hits towards the development of a selective antibiotic.

Publications

Miller, J.C.; Schuler, M.A. Single mutations toggle the substrate selectivity of multifunctional Camptotheca secologanic acid synthases. J. Biol. Chem. 2022, 298, 102237. https://doi.org/10.1016/j.jbc.2022.102237

Miller, J.C.; Hollatz, A.J.; Schuler, M.A. P450 Variations bifurcate the early terpene indole alkaloid pathway in Catharanthus roseus and Camptotheca acuminata. Phytochemistry 2021, 183, 112626. https://doi.org/10.1016/j.phytochem.2020.112626