Nav: Home

Oddball enzyme provides easy path to synthetic biomaterials

May 16, 2017

DURHAM, N.C. - Materials scientists have written the recipe on how to use an oddball enzyme to build new biomaterials out of DNA. The work provides instructions for researchers the world over to build self-assembling molecules for applications ranging from drug delivery to nanowires.

The molecular machinery of the human body typically relies on genetic templates to carry out construction. For example, molecular machines called DNA polymerases read DNA base-by-base to build accurate copies.

There are, however, a few black sheep in the world of molecular biology that do not require a template. One such outlier, called terminal deoxynucleotidyl transferase (TdT), works in the immune system and catalyzes the template-free addition of nucleotides--the building blocks of DNA -- to a single-stranded DNA.

Seemingly random nucleotide sequences in a single DNA strand wouldn't seem to have much of a biological use -- but materials scientists have figured out what to do with it.

In a new paper, Duke University researchers build on their previous work and now describe in detail how the TdT enzyme can produce precise, high molecular weight, synthetic biomolecular structures much more easily than current methods. Researchers can tailor synthesis to create single-stranded DNA that self-assemble into ball-like containers for drug delivery or to incorporate unnatural nucleotides to provide access to a wide range of medically useful abilities.

The results appear online on May 15, 2017 in the journal Angewandte Chemie International Edition.

"We're the first to show how TdT can build highly controlled single strands of DNA that can self-assemble into larger structures," said Stefan Zauscher, the Sternberg Family Professor of Mechanical Engineering and Materials Science at Duke University. "Similar materials can already be made, but the process is long and complicated, requiring multiple reactions. We can do it in a fraction of the time in a single pot."

TdT has advantage over typical, synthetic chain-building reactions in that it continues to add nucleotides to the end of the growing chain as long as they are available. This opens a vast design space to materials scientists.

Because the enzymes all work at the same pace and never stop, the resulting strands of DNA are all very close in size to each other--an important trait for controlling their mechanical properties. The never-ending process also means that researchers can force-feed TdT any nucleotide they want -- even unnatural ones -- simply by providing no other options.

"Your body makes strands of DNA out of only four nucleotides -- adenine, guanine, cytosine and uracil," said Chilkoti, the Alan L. Kaganov Professor and chair of the department of biomedical engineering at Duke. "But we can create synthetic nucleotides and force the enzyme to incorporate them. This opens many doors in making DNA-based polymers for different applications."

For example, unnatural nucleotides can incorporate molecules designed to facilitate "click chemistry" -- enabling the attachment of a whole suite of biomolecules. Researchers can also start the building process with a foundation made of a specific DNA sequence, called an aptamer, which can target specific proteins and cells.

"This enzyme has been around for decades, but this is the first time somebody has mapped these concepts into a blueprint for synthesizing a whole new family of polynucleotides," said Zauscher. "In the past, biochemists have largely been interested in what TdT does in the human immunological system and how it does it. We don't care about all of that, we're just interested in what material building blocks we can make with it. And the precision with which we can make polymers with this enzyme is actually quite exceptional."
-end-
This work was supported by the National Science Foundation (DMR-1411126 and DMR-1121107).

"High Molecular Weight Polynucleotides by Transferase-Catalyzed Living Chain-Growth Polycondensation." Lei Tang, Luis A. Navarro Jr., Ashutosh Chilkoti, and Stefan Zauscher. Angewandte Chemie, 2017. DOI: 10.1002/anie.201700991

Duke University

Related Dna Articles:

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.
Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.
DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.
A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
More DNA News and DNA Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.