Using molecules of DNA like an architectural scaffold, Arizona State University (ASU) scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway, a major breakthrough for future biomedical and energy applications.
Remaking an artificial enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology. To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes. In the middle of the DNA scaffold, a research team led by ASU professor Hao Yan affixed a single strand of DNA, with the molecule called NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes to carry out a chemical reaction
“We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level,” Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry.
“An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature,” said Yan.
The findings were published in the journal Nature Nanotechnology.