Chase Radziej

Nature can accomplish seemingly infinite chemistries despite only having a limited number of building blocks. One way nature accomplishes this is by installing protein-derived cofactors. A recently discovered cofactor is kynurenine (Kyn), an oxidized version of tryptophan that has been utilized in nature for forming unique copper(I)-binding sites. So far, only a few Kyn-containing proteins are known, one of which is MbnP, which is the founding member of the 20243-protein family. MbnP is modified by a tailoring diheme enzyme, MbnH (H-protein), that is responsible for installing Kyn into the protein. These systems are thought to play important roles in copper acquisition and homeostasis, but the rules governing specificity between the “P” and “H” proteins are largely not understood. I aim to test cognate and noncognate interactions, determine what controls cofactor installation, and see whether altering these interactions produces functional copper-binding proteins. This work could help engineer new Kyn-modified proteins and expand the synthetic biology toolkit for studying copper biology.