Evolving enzymes for nonnatural amino acids - C&EN Global

Read the Full Story. Translation Disclaimer Translation of pages on ... Top 5 Most Read ... Support. Get Help; For Advertisers · Institutional Sales; ...
0 downloads 0 Views 91KB Size
Science Concentrates SYNTHETIC BIOLOGY

Evolving enzymes for nonnatural amino acids The N-terminal domain (blue) and the C-terminal domain (white) of pyrrolysyltRNA synthetase bind on opposite sides of the target RNA (brown and orange).

Continuous evolution improves synthetase’s efficiency, selectivity Cells construct their proteins mainly from a collection of 20 canonical amino acids. To study the function of proteins or to give the biomolecules new abilities, biochemists have spent decades finding ways to get cells to move beyond those 20 and use nonnatural amino acids. One method of incorporating nonnatural amino acids into proteins requires biological machinery that can recognize the amino acid and attach it to its corresponding transfer RNA molecule, which a cell’s ribosome then uses to synthesize proteins. A pyrrolysyl-tRNA synthetase (PylRS) from archaea is a favorite for this job because it can be adapted to accept many different nonnatural amino acids but doesn’t recognize the canonical ones. Researchers now report a structure that helps explain why PylRS is so versa-

tile (Nat. Chem. Biol. 2017, DOI: 10.1038/ nchembio.2497). The team then used a protein evolution method with PylRS as a starting point to generate highly active and selective new synthetases (Nat. Chem. Biol. 2017, DOI: 10.1038/nchembio.2474). The research was a collaboration between Dieter Söll’s group at Yale University and David R. Liu’s group at Harvard University. The X-ray crystal structure of PylRS shows that the way it binds a tRNA accommodates the small variable arm of the pyrrolysyl tRNA but not the larger variable arm of canonical tRNAs, explaining why PylRS doesn’t interact with tRNAs that code for canonical amino acids. Liu’s group used PylRS in a protein evolution method called phage-assisted continuous evolution (PACE). The technique improved the efficiency of PylRS as much as

45-fold relative to the parent enzyme. When the researchers made the PACEevolved mutations in other PylRS-derived synthetases, they improved the activity of those enzymes without going through evolution. PACE also evolved synthetases with altered amino acid specificity. “The work presented here allows for aminoacyl-tRNA synthetase (aaRS) evolution over multiple generations on a practical timescale,” says Wenshe Liu, who studies protein evolution at Texas A&M University. “These reports suggest that this new method for aaRS evolution can yield aaRS mutants with considerable improvements in activity and specificity.”—CELIA

ARNAUD

2-D MATERIALS

Photodetectors go 2-D Inside cameras and solar panels, photodetectors absorb light and convert it to useful electronic signals. How well these devices perform depends on how efficiently the detectors can turn incident photons into electrons and corresponding positively charged species called holes. These electron-hole (e-h) pairs can then move through the material to generate electricity. One way to improve this efficiency is to shrink the materials down to the nanoscale. Scientists have used quantum dots, carbon nanotubes, and graphene to achieve efficiencies beyond 100%, meaning a single photon produces more than one e-h pair, an effect known as e-h pair multiplication. Researchers at the University of California, Riverside, led by Nathaniel M. Gabor, now report greater than 300% efficiency with a class of ultrathin two-dimensional

6

C&EN | CEN.ACS.ORG | OCTOBER 23, 2017

materials called transition-metal dichalcogenides. The photodetector is made of two atomic layers of WSe2 stacked on a single layer of MoSe2 (Nat. Nanotechnol. 2017, DOI: 10.1038/nnano.2017.203). The researchers propose that when a photon strikes the top WSe2 layer, it sets an electron in motion that can then hop to the MoSe2 layer to create another e-h pair. By applying a small voltage to the layers, the team was able to further enhance the device’s efficiency to 350%. Work on the 2-D metal dichalcogenides is still in the early stages, Gabor says, but the materials’ efficiencies are “on par” with those of more mature devices made with nanocrystal quantum dots. He adds that one advantage of using dichalcogenides is that they tend to be crystalline, which could make them better

A photodetector device shown sitting on a dime. than quantum dots at electron transport. Pasqual Rivera at the University of Washington says, “with a library of over 1,000 2-D materials, the vast majority of which are yet to be characterized, the prospect of engineering layered nanoscale devices that leverage this understanding for even greater efficiency is highly probable.”—TIEN NGUYEN

C R E D I T: D I E TE R S Ö L L ( 3- D MO D EL ) ; MAX GROS S N I C KLE ( D ET ECTO R )

Stacking transition-metal dichalcogenides improves device efficiency