Millipede Harbors Speedy Catalyst

Stinky millipedes that swarm into houses at night in Japan may hold the key to speedy synthesis of chiral molecules useful for making pharmaceuticals, agrochemicals, and other chemical products. A team of researchers led by Yasuhisa Asano of Toyama Prefectural University found that Chamberlinius hualienensis, a millipede originally from Taiwan that invaded Japan in the 1980s, produces an enzyme called hydroxynitrile lyase that’s much faster at producing enantiomerically pure (R)-mandelonitrile than versions of the catalytic protein used in industry (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1508311112). In millipedes, the enzyme produces smelly hydrogen cyanide from cyanohydrins to serve as a chemical weapon. But, Asano says, industrial chemists run the enzymatic reaction in reverse to make cyanohydrins to produce bulk chemicals, such as acrylamide, as well as drugs, such as clopidogrel, a platelet aggregation inhibitor. Researchers have studied hydroxynitrile lyases for about a century, typically sourcing them from bacteria and plants. The millipede enzyme is “by far the fastest” hydroxynitrile lyase reported to date, comments Anton Glieder, a researcher at Graz University of Technology, in Austria. Additionally, the highly specific production of (R)-mandelonitrile—with 99% enantiomeric excess—is “really astonishing,” he says. Industrial researchers will certainly want to consider the millipede enzyme, Glieder adds.