Nature uses the 20 canonical amino acids as the building blocks to make proteins by combining their sequences to create complex molecules that perform biological functions.
But what happens with arrays immortality chosen by nature? And what possibilities lie in constructing entirely new sequences for making novels? new, Proteins that bear little resemblance to anything in nature?
That’s where Princeton University’s Hecht Lab works. And recently, their interest in designing their own sequences has paid off.
They discovered the first thing known de novo protein that catalyzes or directs the synthesis of quantum dots. Quantum dots are fluorescent nanocrystals used in electronic applications, from LED displays to solar panels.
Their work opens the door to making nanomaterials more sustainably, by showing that non-nature-derived protein sequences can be used to synthesize functional materials and have obvious benefits to the environment.
Quantum dots are normally made in industrial environments with high temperatures and toxic, expensive solvents – this is neither an economical nor an environmentally friendly process. However, Hecht Lab researchers removed the process on the bench using water as the solvent and achieved a stable end product at room temperature.
“We’re interested in making life molecules, proteins, that don’t occur in life,” said Michael Hecht, Professor of Chemistry, who led the research with Greg Scholes, William S. Tod Professor of Chemistry and head of the department. “We’re asking in some ways, are there alternatives 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 come from a common ancestor, can they do amazing things?”
“So here we are making new proteins that never appeared in life by doing things that didn’t exist in life.”
The team’s process can also adjust the nanoparticle size, which determines the glow or fluorescence of color quantum dots. This includes possibilities to label molecules within a biological system, such as staining cancer cells. in vivo
“Quantum dots have very interesting optical properties because of their size,” said Yueyu Yao, a co-author of the paper and a fifth-year graduate student at Hecht Laboratory. “They are very good at absorbing light and converting it into chemical energy – which makes them useful for turning into solar panels or any type of photosensor.
“But on the other hand, they are also very good at emitting light at a certain desired wavelength, which makes them suitable for making LED displays.”
And because they’re small — only about 100 atoms and maybe 2 nanometers in diameter — they can overcome some biological barriers, making their use in medicine and biological imaging particularly promising.
Research, “A de novo protein catalyzes synthesis of semiconductor quantum dots”, published this week Proceedings of the National Academy Sciences (PNAS).
Why use de novo proteins?
“I think use de novo “Proteins are opening a path for designability,” said Leah Spangler, lead author of the study and a former postdoc at the Scholes Lab. “The keyword for me is ‘engineering’. I want to be able to engineer a protein to do a certain thing, and this is the type of protein you can do that.
“The quantum dots we’re making are not of very high quality yet, but they can be improved by tuning the synthesis,” he added. “By designing the protein to affect quantum dot formation in different ways, we can achieve better quality.”
Based on work by Hecht Lab senior chemist and corresponding author Sarangan Chari, the team de novo He designed a protein he named ConK to catalyze the reaction. Researchers first isolated ConK from a large library of binding proteins in 2016. It’s still made from natural amino acids, but “de novo“Because its sequence is nothing like a natural protein.
The researchers found that ConK ensured its survival. coli suggesting that it may be useful for metal bonding and separation at otherwise toxic copper concentrations. The quantum dots used in this research are made of cadmium sulfide. Cadmium is a metal, so the researchers wondered if ConK could be used to synthesize quantum dots.
His premonitions worked. ConK breaks down cysteine, one of the 20 amino acids, into various products, including hydrogen sulfide. This acts as a source of active sulfur, which will then react with the metal cadmium. The result is CdS quantum dots.
“To make a cadmium sulfide quantum dot, you need a source of cadmium and a source of sulfur to react in solution,” Spangler said. “What the protein does is make the sulfur source slowly over time. So we initially add cadmium, but the protein produces sulfur, which then reacts to form quantum dots of different sizes.”
This research was supported by the National Science Foundation MRSEC program (DMR-2011750), Princeton University Writing Center, and the Canadian Advanced Research Institute. Research was also supported by NSF grant MCB-1947720 to MH.