World’s smallest chemical reactor – Built from a single protein inside bacteria

November 01, 2018

In a living cell, hundreds to thousands different chemical reactions take place in parallel. However, many chemical reactions produce reactive or toxic compounds that could harm or even kill a cell. How do organisms protect themselves against such toxic intermediates? Now, scientists from the Max Planck Society discovered that some cells produce proteinaceous nano-reactors inside which they perform hazardous chemical reactions.

Atomic structure of Propionyl-CoA synthase and its three parts

A team around Tobias Erb at the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany studied the bacterial enzyme propionyl-CoA synthase, which catalyzes three different reactions. One of these reactions produces the reactive compound acrylyl-CoA, which is chemically similar to acrylamide, a hazardous compound that has gained world-wide attention in the early 2000s. The Max Planck researchers became interested in understanding how bacterial cells that use propionyl-CoA synthase protect themselves against the toxic acrylyl-CoA formed by the enzyme.

“When we obtained the atomic structure of propionyl-CoA synthase, we were surprised to learn that the enzyme forms a small nano-reactor, which contains a central reaction chamber to sequester acrylyl-CoA”, said Iria Bernhardsgrütter the first author of the study. “Even when we perturbed the reaction sequence of the enzyme, it kept acrylyl-CoA effectively inside without any measurable leakage.”

But how does the nano-reactor control which reaction intermediates to keep inside? The trick is a dynamic regulation. The first reaction of the enzyme induces the closing of the reaction chamber, so that acrylyl-CoA is produced exclusively inside the closed enzyme. The central chamber is only opened again once acrylyl-CoA was converted further into a harmless product.

Cross section through the central reaction chamber of Propionyl-CoA synthase

“It is amazing how nature built this small enzyme reactor that is so sophistically regulated” says Tobias Erb who directed the study. Proteinaceous containers were already known to biologists, but the one discovered by the Max Planck Scientists is by far the smallest one ever reported. With an inner volume of 33 nm3 it is 1024 – or a trillion trillion times – smaller than a soccer ball. Additionally, it shows this precisely controlled opening and closing.

“We now hope to learn more about the building principle of this beautiful biocatalyst” says Erb. “Imagine we were able to build and use such reactors also for the chemical industry. These enzyme reactors could help us to perform challenging chemical reactions in an environmental friendly and sustainable manner in the future” concludes Erb. Besides being supported by the Max Planck Society, the study obtained support from the US Department of Energy, the European Union and Collaborative Research Center 987 of the Deutsche Forschungsgemeinschaft.

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