Nature makes proteins using the 20 canonical amino acids as building blocks, combining their sequences to create complex molecules that perform biological functions.
But what happens to the sequence no natural selection?Build entirely new sequences to make novel or start from scratch A protein that bears little resemblance to anything in nature?
That’s the domain of work in Hecht’s lab at Princeton University. More recently, their curiosity to design their own sequences has paid off.
They discovered the first known start from scratch Proteins that catalyze or drive the synthesis of quantum dots. Quantum dots are fluorescent nanocrystals used in electronic applications ranging from LED screens to solar panels.
Their work opens the door to more sustainable fabrication of nanomaterials by demonstrating that protein sequences not derived from nature can be used to synthesize functional materials – with significant environmental benefits.
Quantum dots are typically manufactured in industrial settings with high temperatures and toxic, expensive solvents—a process that is neither economical nor environmentally friendly. But researchers in Hecht’s lab performed the process on the bench using water as a solvent, producing a stable final product at room temperature.
“We’re interested in making living molecules and proteins that don’t appear in life,” said chemistry professor Michael Hecht, who led the research with William S. Tod Professor of Chemistry and department chair Greg Scholes. “In some ways, we’re asking, is there an alternative to life as we know it? All life on Earth descended from a common ancestor. But if we make life-like molecules that don’t originate from a common ancestor, can they Do something cool?
“So here we are making new proteins that never existed in life, doing things that don’t exist in life.”
The team’s process also makes it possible to tune the size of the nanoparticles, which determines where the colored quantum dots glow or fluoresce.This opens up the possibility of labeling molecules within biological systems, such as staining cancer cells in vivo.
“Quantum dots have very interesting optical properties because of their size,” said paper co-author Yueyu Yao, a fifth-year graduate student in Hecht’s lab. “They’re very good at absorbing light and converting it into chemical energy — which makes them useful for making solar panels or any kind of light sensor.
“But on the other hand, they’re also very good at emitting light at specific wavelengths, which makes them suitable for making LED screens.”
And because they’re so small—made up of only about 100 atoms and perhaps only 2 nanometers in diameter—they are able to penetrate some biological barriers, making them particularly promising for use in medicine and bioimaging.
The study “A start from scratch Protein-Catalyzed Synthesis of Semiconductor Quantum Dots,” published this week in Proceedings of the National Academy of Sciences Science (Proceedings of the National Academy of Sciences).
Why use de novo protein?
“I think using start from scratch “Proteins have opened up an avenue for designability. For me, the key word is ‘engineering,'” said Leah Spangler, the study’s lead author and a former postdoc in the Scholes lab. I want to be able to design proteins to do specific things , which is a protein you can do with it.
“The quality of the quantum dots we’re making isn’t very good yet, but it can be improved by tweaking the synthesis,” she added. “We can achieve better quality by designing proteins to affect quantum dot formation in different ways.”
Building on work by corresponding author Sarangan Chari, a senior chemist in the Hecht lab, the team used start from scratch It engineered a protein called ConK to catalyze the reaction. Researchers first isolated ConK in 2016 from a large combinatorial library of proteins. It is still made from natural amino acids, but it qualifies as a “start from scratch“Because its sequence doesn’t bear any resemblance to the natural protein.
The researchers found that ConK makes Escherichia coli Among other toxic concentrations of copper, it is suggested that it may be useful for metal binding and sequestration. The quantum dots used in this study are made of cadmium sulfide. Cadmium is a metal, so the researchers wondered if ConK could be used to synthesize quantum dots.
Their hunch paid off. ConK breaks down cysteine, one of the 20 amino acids, into a variety of products, including hydrogen sulfide. It acts as an active sulfur source, which then goes on to react with metallic cadmium. The result is CdS quantum dots.
“To make cadmium sulfide quantum dots, you need a cadmium source and a sulfur source to react in solution,” Spangler said. “What the protein does is slowly generate a source of sulfur over time. So, we initially add cadmium, but the protein generates sulfur, which then reacts to generate quantum dots of different sizes.”
This research was supported by the National Science Foundation’s MRSEC program (DMR-2011750), the Writing Center at Princeton University, and the Canadian Institute for Advanced Study. This research was also supported by NSF grant MCB-1947720 awarded to MH.
