New hybrid nanocages for better catalytic efficiency

The cage was designed with amino acid replacements by introducing site-specific mutations that allowed greater uptake of IrCp*. Credit: Takafumi Ueno of the Tokyo Institute of Technology

A new hybrid ferritin nanocage with histidine residues shows 1.5 times higher metal ion uptake and improved catalytic efficiency for alcohol production, according to Tokyo Tech researchers in a new study. Their findings suggest that hybrid bio-nanocages could efficiently catalyze reactions to produce industrially important products.

Biological polymers can spontaneously self-assemble into complex structures that look like vessels or cages, but are much smaller and are called “nano-cages”. These structures can accommodate a wide range of molecules inside that behave like “guests”. A popular example is ‘ferritin nanocage’, which is formed by the self-assembly of 24 subunits in the protein ferritin and may contain metal ions which are important catalysts. With the help of these metal ions, a catalytic reaction converts any substrate into a product. Although widely known, the potential applications of the ferritin cage in industry have yet to be fully explored.

So far, most efforts to increase metal ion uptake in ferritin have resulted in cages with poor stability. In order for the “guest” to sit comfortably in the cage, efficient design is key. Keeping this in mind, a team of scientists led by Professor Takafumi Ueno, from the Tokyo Institute of Technology, Japan (Tokyo Tech), introduced site-specific mutations to the core of the ferritin nanocage and increased its absorption of the iridium complex (IrCp* ). Their findings are published in Angewandte Chemie. Iridium is an essential catalyst in the alcohol production pathway and is used commercially in the pharmaceutical, food and chemical industries.

Hybrid Bio-Nanocage Formed by Ferritin Protein

The nanocage acts as a hybrid biocatalyst when converting substrates into high specificity alcohols. Credit: Takafumi Ueno of the Tokyo Institute of Technology

Professor Ueno explains: “Based on previous literature, we knew that the presence of coordination amino acids in the cage enhance iridium activity, and that replacing these amino acids with appropriate residues might alleviate the problem. Since the iridium complex behaves like a catalyst, coordination residues would do the trick. The authors used the amino acid histidine to replace two residues, arginine and aspartic acid of the regular (wild-type) ferritin cages and create the R52H and D38H mutants. Remarkably, the assembly structure or cage size were not affected by these changes.

Next, they added IrCp* to the mutants and found that R52H was able to integrate 1.5 times more iridium atoms than the wild-type cage (Figure 1). But, what struck them was the mutant D38H, which behaved exactly like the wild type! So why didn’t the two mutations have the same effect? According to Professor Ueno, “this implies that it is not only the presence of the histidine residue but also its position that is crucial in determining the efficiency of uptake in the cage”.

Using the new catalytic cages, researchers were able to achieve alcohol production rates as high as 88%. Obviously, the mutations promoted a structural rearrangement of the reaction components, which improved the conversion rate (Figure 2).

To understand how the substrate behaved inside the cage, the researchers used simulations in which the substrate molecules could move freely within the nanocage. They observed some interactions between the substrate and histidine in the R52H mutant, which were not present in the wild-type cage, i.e., the substrate showed preferential binding in the nanocage.

“These hybrid bio-nanocages were also found to be very stable, suggesting that they could be used as viable catalysts in industrial applications,” concludes Professor Ueno. The current structure-based design of metal ion binding site research could be advanced to create novel ferritin mutants with selective uptake of specific guest molecules, for varied catalytic applications in chemical and pharmaceutical industry.

Reference: “Controlled Uptake of an Iridium Complex inside Engineered apo-Ferritin Nanocages: Study of Structure and Catalysis” by Mohd Taher, Basudev Maity, Taiki Nakane, Satoshi Abe, Takafumi Ueno and Shyamalava Mazumdar, January 10, 2022, Angewandte Chemie.
DOI: 10.1002/anie.202116623

Irene B. Bowles