Atomistic-level Insights into the Role of Mutations in Engineering of PET hydrolases: A Systematic Review

Plastic pollution is a growing global challenge and traditional plastic waste management methods are proving inadequate in tackling the issue. Enzymatic biodegradation has emerged as a promising alternative to plastic waste management due to its environmentally friendly profile. Polyethylene terephthalate (PET) is among the most widely used polymers in packaging and recent research has identified several PET-degrading enzymes, such as TfCut2, IsPETase and LCC, as promising candidates for biodegradation applications at the industrial level. This has led to extensive efforts for improving their catalytic efficiency, with targeted mutagenesis being the preferred method employed for their modification. To this end, molecular dynamics (MD) simulations coupled to experimental validation have provided critical atomistic-level insights into the effect of mutations on enzymatic function. The present systematic review examines the role of mutations in enzymatic activity and thermostability, analyzing their structural and mechanistic contributions across 20 studies. The integration of MD simulations to experimental findings allows the elucidation of the mechanistic details governing polymer degradation, as well as the identification of key residue and enzyme hotspots that enhance catalytic performance. The review further highlights the role of MD simulations as powerful tools in providing valuable insights towards guiding targeted mutations for enzyme efficiency optimization.