The coupling of enzymatic and heterogeneous catalysis is promising to develop new cascade processes for green chemical manufacture. Due to the optimal conditions for enzymes and chemical catalysts are often quite different and even contradictory in some cases, the incompatibility between these two types of catalysis is a challenge for the one-pot cascade reactions. In general, enzymatic catalysis takes place under mild conditions such as aqueous solution, ambient temperature and pressure. However, the reactions catalyzed by heterogeneous catalysts in these conditions are very lacking, because heterogeneous catalysts especially metals often display low activities at low temperatures and sensitive to oxygen as well as water. We aimed at rationally designing an enzyme-metal hybrid catalyst with both high enzymatic and chemical catalytic efficiency under a relatively mild condition. 

In recent years, the size-dependent activity of metal nanoparticles is attracting growing interest. The morphology and electronic structure of particles and the metal-support interactions will significantly change as the metal particles downsizing from nanometer to sub-nanometer, which may greatly enhance their activity. Combining enzymes and metal sub-nanoparticles might be a good approach to realize the one-pot cascade reactions under mild conditions. Based on this assumption, we synthesized an enzyme-metal hybrid catalyst with controllable metal nanoparticle size by using a single protein-polymer conjugate as the confined nanoreactor. In this manner, the aggregation of Pd nanoparticles can be avoided effectively, which is different from using the protein alone as the template. In the experiment, a temperature-responsive polymer Pluronic was selected for the synthesis of enzyme-polymer conjugates based on our previous findings that the enzyme-Pluronic conjugates are readily soluble and monodispersed in organic solvents. The entanglement of Pluronic around protein was revealed by molecular dynamics (MD) simulations and the nano-electrospray ionization mass spectrometry (nanoESI-MS). We were surprised to find that a single Pd nanoparticle can be in situ reduced and stabilized in a single protein-polymer conjugate with the assistance of the confined space between enzyme and polymer layer. 

An obvious size-dependent activity of Pd nanoparticles was observed. In addition, the Pd sub-nanoparticles exhibited dramatically increased activity at the optimum temperature of lipase (55 ^oC). The activity of 0.8 nm Pd nanoparticles was more than 50 times that of commercial Pd/C in the racemization of (S)-1-phenylethylamine. We found that more Pd-O coordination was presented as the size of Pd changed from nanometer to sub-nanometer. This increased proportion of Pd-O coordination is essential for the high activity of Pd sub-nanoparticles at low temperatures due to the partial oxidation of Pd surface results in a lower desorption energy than the unoxidized one, which was confirmed by density functional theory (DFT) calculations. The enzyme-metal nanohybrids (Pd/CALB-P) displayed high activity in the dynamic kinetic resolutions of pharmaceutical intermediates. The strategy for constructing enzyme-metal hybrid catalysts with good compatibility between enzymatic and metal-catalytic activities provides many potential applications in chemical industry.

To learn more about this work, please check out our article "Highly active enzyme–metal nanohybrids synthesized in protein–polymer conjugates" published in Nature Catalysis. 

Written by Xiaoyang Li and Jun Ge

https://www.nature.com/articles/s41929-019-0305-8