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Increasing the Soluble Expression and Whole-Cell Activity of the Plastic-Degrading Enzyme MHETase through Consensus Design

Proceedings of the Karelian Research Centre of the Russian Academy of Sciences 2024 10 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Jake Saunders, Adam M. Damry, Vanessa Vongsouthi, Matthew A. Spence, Rebecca L. Frkic, Chloe Gomez, Patrick Yates, Dana S. Matthews, Nobuhiko Tokuriki, Malcolm D. McLeod, Colin J. Jackson

Summary

Using consensus sequence design, researchers engineered improved variants of MHETase, an enzyme that breaks down a key intermediate in PET plastic degradation. The best variants achieved more than 10-fold higher whole-cell activity compared to the wild type, primarily by enhancing soluble protein expression and correct folding. These findings demonstrate a practical engineering strategy for boosting the industrial potential of plastic-degrading enzymes.

Polymers

The mono(2-hydroxyethyl) terephthalate hydrolase (MHETase) from Ideonella sakaiensis carries out the second step in the enzymatic depolymerization of poly(ethylene terephthalate) (PET) plastic into the monomers terephthalic acid (TPA) and ethylene glycol (EG). Despite its potential industrial and environmental applications, poor recombinant expression of MHETase has been an obstacle to its industrial application. To overcome this barrier, we developed an assay allowing for the medium-throughput quantification of MHETase activity in cell lysates and whole-cell suspensions, which allowed us to screen a library of engineered variants. Using consensus design, we generated several improved variants that exhibit over 10-fold greater whole-cell activity than wild-type (WT) MHETase. This is revealed to be largely due to increased soluble expression, which biochemical and structural analysis indicates is due to improved protein folding.

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