Rate-enhancing PETase mutations determined through DFT/MM molecular dynamics simulations

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Jerves, C (Author) Other; Neves, RPP (Author) FCUP; da Silva, SL (Author) Other; Ramos, MJ (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: New Journal of Chemistry

Vol. 48

Pages: 45-54

ISSN: 1144-0546

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00Z-E3M

DOI: 10.1039/d3nj04204a

Abstract (EN): The PETase enzyme from the bacterium Ideonella sakaiensis can degrade polyethylene terephthalate (PET) back into its polymeric constituents at room temperature, making it an ecologically friendly tool for reducing PET pollution. Computational enzyme optimization is a fundamental tool to accelerate enzyme engineering towards the green revolution promised by the introduction of enzymatic catalysis in industry. The Asp83Asn mutant generates a sub-optimal reactive conformation that the mutation-induced transition state stabilization does not compensate for, and the barrier is raised by 1.9 kcal mol-1. In contrast, the Asp89Asn mutant keeps a perfect reactive conformation, and the mutation stabilizes the transition state more than the reactants, lowering the barrier by 4.7 kcal mol-1. We show that computer-based well-chosen single-residue substitutions in PETase can decrease the activation barrier significantly, facilitating the development of highly-efficient PETase mutants. The results of this work encourage future studies that aim for rational enzyme engineering on PETase and other enzymes. The PETase enzyme from the bacterium Ideonella sakaiensis can degrade polyethylene terephthalate (PET) back into its polymeric constituents at room temperature, making it an ecologically friendly tool for reducing PET pollution.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10