Benjamin Royer, Yuta Era, Marcos Valenzuela-Ortega, Thomas W. Thorpe, Connor L. Trotter, Kitty Clouston, John F. C. Steele, Nicoll Zeballos, Eugene Shrimpton-Phoenix, Bhumrapee Eiamthong, Chayasith Uttamapinant, Christopher W. Wood, Stephen Wallace
Abstract Using engineering biology to perform complex chemical synthesis offers a sustainable alternative to traditional processes that rely on finite fossil resources. A growing opportunity within this field lies in reclaiming carbon embedded in industrial and post-consumer waste—carbon otherwise lost to landfill, incineration or pollution. Here we report the bio-upcycling of poly(ethylene terephthalate) (PET) plastic waste into levodopa ( l -DOPA), a frontline medication for Parkinson’s disease, using engineered Escherichia coli . Two key bottlenecks—substrate import and feedback inhibition by the intermediate protocatechuate—were addressed through heterologous transporter expression and functional pathway separation across two microbial strains. To further improve sustainability, and as a proof-of-concept, Chlamydomonas reinhardtii was used to capture CO 2 released during catechol generation. The resulting bioprocess operates under mild, aqueous conditions and achieves high l -DOPA titres (5.0 g l −1 ), with isolated product obtained at preparative scale from both industrial PET waste and a single post-consumer plastic bottle. This work demonstrates how engineering biology can transform plastic-derived aromatic monomers into high-value pharmaceuticals for the treatment of neurological disease in humans.