Engineered polyketide synthases enable a microbial chassis for recyclable plastics with tunable properties.

Wang, Zilong; Cheong, Seokjung; Wang, Hai; Demarteau, Jeremy; Epstein, Alexander R; Bose, Baishakhi; Hu, Weixi; Schmidt, Matthias et al. · Nat Biotechnol · 2026

basic_science · Level V

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Abstract

Plastics derived from fossil feedstocks pose major recycling challenges, particularly crosslinked thermosets used in electronics, construction and composites. Polydiketoenamines (PDKs) are recyclable alternatives; however, monomers such as dimedone are petrochemical-derived and offer limited tunability. We computationally screened 144 β-keto-δ-lactones (BKDLs), identifying solvation free energy as the primary determinant of depolymerization temperature across a 20-60 °C range. We engineered hybrid type I polyketide synthases (PKSs) in Escherichia coli and Streptomyces hosts to biosynthesize BKDLs with diverse substituents and defined stereochemistry, reaching titers of 1.84 g L<sup>-1</sup> in bioreactors. Polymerization of chemically synthesized BKDLs identical to PKS products confirmed tunable glass transition temperatures (53-98 °C) and temperature-gated depolymerization. Different BKDLs yielded PDKs with thermal, mechanical, solvent-resistance and optical properties governed by substituent and chirality. Technoeconomic and life-cycle analyses indicate that corn-stover-derived BKDLs can outperform petrochemical dimedone on cost and greenhouse gas emissions. This study demonstrates that engineered PKSs can produce monomers for recyclable plastics with programmable depolymerization behavior.