Inorganic Seminar - Yasunori Okamoto

The Inorganic Seminar Series presents: Yasunori Okamoto

Exploratory Research Center on Life and Living Systems (ExCELLS)

Host: Yi Lu

Title: Harnessing Proteins as Reaction Compartments and Ligands: Artificial Metalloenzymes toward Biochemical Applications

Location: WEL 2.122

Refreshments served at 3:15pm

Artificial metalloenzymes (ArMs) are constructed either by introducing a synthetic metal complex into a protein or by designing an abiological metal center within one. They have been developed with two main motivations: as functional models for the mechanistic study of natural metalloenzymes that are difficult to isolate, and as catalysts that achieve highly selective transformations in water under mild conditions. 

Our group pursues a complementary direction, systems catalysis, in which an ArM serves as a catalytic module that implements an abiological transformation within a system composed of multiple biomolecules. We have previously shown that ArMs can be coupled with natural enzymatic reaction networks and can even operate inside mammalian cells. Pushing this further, however, requires enzymes designed for biochemical contexts from the outset, and in such settings the protein is asked to play three roles: a reaction compartment that controls the reactivity of the incorporated catalyst, a ligand that defines the metal center, and a shield that protects the abiotic cofactor from biomolecules. 

In this presentation, I will discuss two new ArMs that exploit these roles. In the first part of this talk, I will describe a photocatalytic ArM in which the protein acts as a reaction compartment to control the excited-state reactivity of an incorporated ruthenium complex. Encapsulation switches the dominant pathway from photoredox catalysis to energy-transfer catalysis, enabling amino-acid-selective protein modification. In the second part, I will present an ArM in which the protein itself serves as the ligand. Through computational design, we constructed a cytokine-based designer enzyme bearing an abiological multinuclear metal center coordinated solely by amino-acid side chains. With biochemical applications in mind, we explore how an extrinsic catalytic function can be added to a protein while retaining its intrinsic one.