Tokyo University of Agriculture and Technology Biomolecular Engineering & Marine Biotechnology Lab.
Development of functional bionanomaterials
Magnetic particulates biosynthesized by magnetotactic bacteria
As single-domain nanomagnets are coated by lipid bimolecular membrane and can be magnetically recovered easily from bacterial lysate through external magnetic field, magnetic particulates synthesized by magnetotactic bacteria intracellularly possess a more superior dispersibility than artificial magnetites. By using these characteristics, the development of high-sensitivity immunoassay used as the magnetic immobilization carrier of antibodies, as well as the application in the magnetic carrier of drug delivery system, have been done. Moreover, the technology of targeting foreign proteins to the surface of magnetic particulates through the genetic modification of magnetotactic bacteria has been established (magnetosome display system), and the production of protein-magnetic particulate complexes using magnetotactic bacteria can now be achieved more easily and at a lower cost. In addition, the development of various protein-magnetic particulate complexes based on genetic design is undergoing.
Magnetosome display system
Through recombinant DNA technology, magnetotactic bacteria can be used as the producing host of foreign proteins, just like foreign protein-producing hosts such as E. coli. The difference between magnetotactic bacteria and other foreign protein-producing hosts is their ability to display foreign proteins on the surface of magnetic particulates. Mms13 protein, which has the highest localization amount among all magnetite-binding proteins, bond strongly to magnetites and can be used as the “anchor molecule” of various target proteins. It is now possible to develop the underlying technology of “magnetosome display system”, which creates functional magnetic particulates by transporting target proteins to the surface of magnetic particulates using this Mms13 proteins, and to freely control the surface of magnetic particulates. By modifying the genes of target proteins, it is possible to display various proteins on the surface of magnetic particulates using the same method. In addition, we are developing the technology for tagging, isolating, detecting and screening biomolecules in the blood and the environment through functional magnetic particulates produced through this system.
Creation of membrane receptor-magnetic particulate complexes for drug discovery
Membrane proteins are important drug discovery targets, and novel drugs are developed by screening compounds that bind to these membrane proteins. Therefore, the efficient production of membrane proteins and the technology of evaluating compound binding in a high-throughput manner are important for the construction and cost reduction of the drug discovery process. Our laboratory is developing magnetic particulates that display membrane proteins by using the magnetosome display system. So far, we have succeeded in the functional expression of CD81, a transmembrane protein involved in the infection mechanism of hepatitis C virus, thyroid-stimulating hormone receptor (THSR), a G protein-coupled receptor, and TrkA, the tyrosine kinase receptor related to mental diseases such as the Alzheimer’s disease and depression. With this technological development, we have so far succeeded in producing the target protein-magnetic particulate complex shown below. This target protein-magnetic particulate complex can magnetically recover only specific substances that bind with functional proteins from the reaction liquid efficiently. This principle is applicable to a wide range of areas, such as for the detection of estrogen-like substances from environmental water samples, and the isolation of target cells from blood.
