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Mitchell Lab

Recent News

Doug will be presenting at ICSB2026 in San Francisco on preclinical development of RiPPs!

Congrats to Will H for passing his Qualifying exam!

Congrats to Salimat for passing her Qualifying Exam!

Welcome to our first round rotation students, Sophie and Angelica!

Dominic will deliver an oral presentation at the Biochemistry retreat on Oct 10!

From Genes to Molecules

Illustration showing the relationship between DNA, protein structure, and a small molecule: a DNA double helix on the left points via an orange arrow to a folded protein ribbon structure on the right, which then points via another arrow to a linear chemical structure at the bottom.We are a chemical biology group that focuses on the study of natural products. Natural products are highly evolved and functionally privileged compounds that often display complex chemical structures. These molecules have inspired generations of synthetic organic chemists, unveiled numerous fundamental biological processes as chemical probes, and served as the most significant source of chemical matter for drug discovery.

As the field of genomics has expanded, it has revealed a vast untapped wealth of natural products encoded in the DNA of sequenced organisms, particularly bacteria. Our lab has developed new tools to expedite the discovery of natural products from genomic information, including molecules from bacteria that cannot be cultivated in a lab. In particular, our lab focuses on Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) which have genetically encoded substrates and an incredible diversity of post-translational modifications. Using a genes-to-molecule approach, we have uncovered numerous structurally unique RiPP molecules and revealed the unprecedented mechanistic enzymology through which they form.

We can then leverage this knowledge to produce new-to-nature compounds with improved properties or novel activity with the long-term goal of unleashing the full synthetic potential of Nature to reshape the diagnosis and treatment of human disease.

Yanqing, with Markus Voehler of the Vanderbilt Center for Structural Biology, published an article in Angewandte Chemie International Edition identifying the sulfur donor for YcaO-catalyzed thioamidation of ribosomal protein uL16. Screening E. coli sulfur donor deletion strains showed that only loss of IscS, the cysteine desulfurase of iron-sulfur cluster assembly, abolished the modification, and in vitro reconstitution with IscS and cysteine was 20-fold more catalytically efficient than free sulfide.

Austin and collaborators from the Broderick and Guo labs have published an article in ACS Bio & Med Chem Au investigating an archaeal radical SAM enzyme that modifies a cysteine-rich protein.

Dinh and collaborators from the van der Donk lab published an article in Angewandte Chemie International Edition on ApyO, the cytochrome P450 that macrocyclizes the aminopyruvatide precursor peptide.

Riley and collaborators from the Mitchell lab published an article in ACS Chemical Biology about the discovery and characterization of several examples of partner protein-dependent graspetide biosynthesis.

Andrew and Yanqing, along with past and present members of the lab, have published a paper in ACS Biochemistry identifying the activity of E. coli’s YcaO enzyme: thioamidation of ribosomal protein uL16.

Mayuresh and Miriam along with several former lab members (Shravan, Alex, and Xiaopeng) published an article in ACS Chemical Biology exploring a widespread group of multinuclear nonheme iron-dependent oxidative (MNIO) enzymes that modify peptide substrates.