Engineered polyketide synthases enable a microbial chassis for recyclable plastics with tunable properties
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 −1 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.
Authors
- Jay D. Keasling (ORCID: https://orcid.org/0000-0003-4170-6088)
- Nemi Vora (ORCID: https://orcid.org/0000-0002-7359-6728)
- Baishakhi Bose (ORCID: https://orcid.org/0000-0002-6309-0088)
- Mei Zhao (ORCID: https://orcid.org/0000-0002-5762-6552)
- Hai Wang (ORCID: https://orcid.org/0000-0002-1215-2613)
- Brett A. Helms (ORCID: https://orcid.org/0000-0003-3925-4174)
- Nawa Raj Baral (ORCID: https://orcid.org/0000-0002-0942-9183)
- Corinne D. Scown (ORCID: https://orcid.org/0000-0003-2078-1126)
- Christopher J. Petzold (ORCID: https://orcid.org/0000-0002-8270-5228)
- Alexander R. Epstein (ORCID: https://orcid.org/0000-0002-9914-2388)
- Kristin Aslaug Persson (ORCID: https://orcid.org/0000-0003-2495-5509)
- Edward E. K. Baidoo (ORCID: https://orcid.org/0000-0001-5787-1219)
- Seokjung Cheong (ORCID: https://orcid.org/0000-0002-5699-2278)
- Alberto A. Nava (ORCID: https://orcid.org/0000-0002-0172-4145)
- Beibei Ge (ORCID: https://orcid.org/0000-0002-7365-9872)
- Kevin Yin (ORCID: https://orcid.org/0000-0002-3639-1125)
- Yuzhong Liu (ORCID: https://orcid.org/0000-0001-5614-1951)
- Zilong Wang (ORCID: https://orcid.org/0000-0002-4414-9494)
- Robert W. Haushalter
- Pablo Cruz‐Morales (ORCID: https://orcid.org/0000-0002-6751-8897)
- Yifan Guo (ORCID: https://orcid.org/0009-0001-2966-7138)
- Jérémy Demarteau (ORCID: https://orcid.org/0000-0002-0311-3575)
- Sarah Nordahl (ORCID: https://orcid.org/0000-0002-6870-4755)
- Leah S. Keiser (ORCID: https://orcid.org/0009-0005-1098-655X)
- Rithwik Ghanta
- Yan Chen (ORCID: https://orcid.org/0000-0002-1125-313X)
- Matthias Schmidt (ORCID: https://orcid.org/0000-0002-3363-4777)
- Ramu Kakumanu
- Weixi Hu
Institutions
- Jiangsu University (CN)
- Amazon (United States) (US)
- Berkeley College (US)
- Lawrence Berkeley National Laboratory (US)
- University of Illinois Urbana-Champaign (US)
- Durham University (GB)
- Novo Nordisk Foundation (DK)
- Energy Biosciences Institute (US)
- Institute of Plant Protection (CN)
- Dow Chemical (United States) (US)
- Institute for the Future (US)
- Chinese Academy of Agricultural Sciences (CN)
- Joint BioEnergy Institute (US)
- University of California, Berkeley (US)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2026-07-27
- DOI
- https://doi.org/10.1038/s41587-026-03229-7
- Primary Topic
- biodegradable polymer synthesis and properties
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- U.S. Department of Energy
- Office of Science
- Basic Energy Sciences
- Biological and Environmental Research
- Bioenergy Technologies Office