Recent Insights and Future Perspectives on Promiscuous Hydrolases/Acyltransferases

Promiscuous hydrolases/acyltransferases have attracted attention for their ability to efficiently catalyze selective transacylation reactions in water to produce esters, thioesters, amides, carbonates, and carbamates. Promiscuous hydrolases/ acyltransferases can be implemented into aqueous enzyme cascades and are ideal biocatalysts for the acylation of hydrophilic substrates that are barely soluble in dry organic solvents. This activity was thought to be rare, and recent research has focused on just a small number of accidentally identified promiscuous hydrolases/acyltransferases. High-throughput screening for acyltransferases and an in silico sequence-based method for prediction of acyltransferase activity provided access to many efficient promiscuous hydrolases/acyltransferases, thereby demonstrating that promiscuous acyltransferase activity is rather common in hydrolases. These synthetically valuable enzymes could further be enhanced by protein engineering. This Perspective aims to demonstrate the synthetic potential of these enzymes and raise awareness of the frequency of this activity.

Automated summary

Promiscuous hydrolases/acyltransferases are efficient in catalyzing selective transacylation reactions in water, forming various compounds. Through high-throughput screening and sequence-based prediction, many efficient enzymes have been discovered, indicating that this activity is common in hydrolases and has synthetic potential.