Category: Biologics Discovery

1339-E - Making Ferritin Faster

Wednesday, February 7, 2018
11:30 AM - 12:30 PM

Ferritins are enzymes that are capable of storing iron for metabolic purposes, used by nearly all living things. In our ongoing quest to unveil the mechanism behind the unique bioluminescence process in the marine tube worm Chaetopterus sp. and its secreted mucus, we have recently discovered a ferritin that takes up iron faster than all other previously described ferritins. The presence of ferritin in the bioluminescent mucus was particularly interesting because the bioluminescence is stimulated in vitro by addition of Fe(II). Thorough enzyme characterization revealed that Chaetopterus ferritin (ChF) acts up to 8 times faster than the recombinant human heavy chain ferritin (HuHF) we used as a reference. It is critical to study and understand this highly performing ferritin for its function in the bioluminescence as well as for engineering purposes and applications. Based on the crystal structure of ChF in comparison with crystal structures available for HuHF and other ferritins, a number of interesting residues were identified that could cause the increased speed. We here present the results of a comparative mutation study on ChF and HuHF. Four mutations in and near active sites were investigated for their effect on the velocity of the ferritins’ iron uptake. In HuHF, three of the mutations were found to significantly increase the enzyme velocity indeed, while in ChF two did not affect the velocity at all. We believe that the transport of iron from the entrance into the ferritin cage to the active (ferroxidase) site is facilitated by these mutations and at least partially responsible for the enzyme activity improvement of ChF over HuHF. Ferritin could therefore be made faster, which could benefit several applications of ferritins in biotechnology. The applied interests of this ferritin are diverse and targeting environmental applications for removing contaminants from aquatic systems as well as public health since ferritin is often used for targeted drug delivery inside the body but also is a key player against viral infections. Our communication will present the details of our work on the amino acid structure-function relationship, and on the overall applications in which a “super-ferritin” would be beneficial. 

Evelien De Meulenaere

Postdoctoral researcher
Scripps Institution of Oceanography (UC San Diego)
San Diego, CA

Trained in chemistry and biochemistry at the University of Leuven in Belgium, I followed the path of protein chemistry walking hand in hand with bioinformatics, nonlinear optics and imaging, bio-engineering all the way to marine biology at the Scripps Institution of Oceanography in La Jolla (UC San Diego). I worked on topics ranging from HIV and fluorescent proteins to bioluminescence in marine critters, using my skills in molecular biology, protein expression and purification and a multitude of spectroscopies, microscopies and informatics.