Pushing the bounds of biocatalysis - C&EN Global Enterprise (ACS

Enzymes often elicit envy from organic chemists. Highly evolved by nature, these biocatalysts can carry out reactions with a selectivity that surpasse...
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NEUROSCIENCE

Probe records hundreds of neurons Titanium nitride sensors could enable a revolution in ‘systems neuroscience’ difficult to understand how large networks A probe that can simultaneously record of neurons are connected. electrical signals from hundreds of indiIn contrast, Neuropixels is 1 cm long vidual neurons could reveal how different and covered in a checkerareas of the brain work board pattern of 12-µmtogether to produce wide recording contacts, complex behaviors (Napotentially spanning a ture 2017, DOI:10.1038/ mouse’s entire brain. It nature24636). can simultaneously reThe probe, called Neucord electrical activity in ropixels, is thinner than 384 of these sensors and a human hair and carries switch between sensors 960 microscopic sensors to home in on brain areas made from a unique form of interest. “For the first of titanium nitride—one time in the world, this of several innovations enables ‘systems neuroin materials science that A Neuropixels probe, just 70 science,’ ” says Barundeb were crucial to creating µm wide, is covered with a Dutta, chief scientist at the device. patchwork of titanium nitride nanoelectronics company Conventional neural sensors. Imec, which was part of probes that are used in the large international consortium that delaboratory animals typically have a few veloped the device. dozen sensors and pick up readings from Neuropixels’ cross section of 70 x 20 µm only small regions of the brain, making it

is smaller than conventional probes, making it thin enough to avoid causing damage when inserted into the brains of living animals. Weighing just 250 mg, it can record signals from unrestrained animals for many weeks. Not only can Neuropixels record more than 10 times as many neurons as previous probes, it should also be at least 10 times cheaper, Dutta says. Making the sensors from titanium nitride rather than gold means that the probe is suitable for mass manufacture. The consortium hopes to begin selling Neuropixels next year for the same amount it costs to fabricate them. “It democratizes neuroscience,” Dutta says. Patrick Ruther at the University of Freiburg, who was not involved in the research, believes that it may eventually be possible to interpret the neural signals recorded by one of these next-generation devices and translate a person’s intention to move into action by a robotic prosthetic. “In the long run, I can imagine that devices like these could be used as interfaces between brain and machines,” Ruther says.—MARK PEPLOW, special to C&EN

BIOSYNTHESIS

Pushing the bounds of biocatalysis

C R E D I T: TI M OT H Y H A R R IS LA B /JA N E LI A R ES EA RCH CA MP U S

Chemists conquer challenging oxidative dearomatization reaction using trio of enzymes SorbC—carry out the same reaction (Nat. Chem. 2017, DOI:10.1038/nchem.2879). In the reaction, known as an oxidative dearomatization, a catalyst breaks the aromaticity of a planar ring system to install an oxygen species, forming a valuable chiral building block. Narayan and her team determined which of the three enzymes worked best with which substrates from a group, allowing them to maximize the reaction’s enantioselectivity and site selectivity and enabling the chemists to target specific positions and geometries OH O OH around the ring. R1 O TropB or R1 Previous catalytic methods for R4 AzaH, O2 R4 HO oxidative dearomatizations have O HO R3 R3 struggled to achieve high selectivity, R2 R2 often wasting chiral oxidants like hypervalent iodine reagents and R1 = alkyl; R2 = H, alkyl, NO2; R3 = alkyl, aryl; R4 = H, alkyl metal complexes in the process. The enzyme-driven reaction, on the other A sampling of the oxidative dearomatizations hand, uses a more atom-economical carried out by enzymes TropB and AzaH.

Enzymes often elicit envy from organic chemists. Highly evolved by nature, these biocatalysts can carry out reactions with a selectivity that surpasses most synthetic catalysts. Yet they tend to act on such a narrow range of substrates that chemists haven’t been able to exploit their abilities in a general way. In an effort to broaden enzymes’ reach, researchers led by Alison Narayan at the University of Michigan explored how three known enzymes—called TropB, AzaH, and

reagent, molecular oxygen. Under the conditions needed for synthetic oxidative dearomatizations, products can undergo undesirable side reactions, whereas under the enzymatic reaction conditions, products are stable, Narayan says. By using freeze-dried cells, which lasted in a freezer for six months without the enzymes inside losing reactivity, the researchers could also run the enzyme reactions at a scale that’s practical for synthetic chemists. “This is a great example of how enzymes can effect difficult transformations in chemical synthesis,” says Frances H. Arnold, a biosynthesis pioneer at California Institute of Technology. “Starting from newly-discovered enzyme activities, Narayan and coworkers leveraged nature’s diversity to assemble and demonstrate a versatile platform for site- and stereoselective oxidative dearomatization, all the way to the gram scale.” The team plans to further probe the enzymes’ chemistry with an eye toward eventually engineering the biocatalysts for a broader range of reactions.—TIEN NGUYEN NOVEMBER 20, 2017 | CEN.ACS.ORG | C&EN

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