A Metabolically Integrated Lossen Rearrangement in Escherichia coli

Biocompatible chemistry enables abiotic reactions to be interfaced with metabolic pathways in living microorganisms. This includes both native and de novo biosynthetic processes to access abiotic feedstocks, intermediates and products in vivo. Herein we report a biocompatible Lossen rearrangement that is catalysed by phosphate in the bacterium Escherichia coli for the chemical transformation of activated acyl hydroxamates to primary amines in living cells. Using a para-carboxylated substrate, the biocompatible reaction can be used to generate the metabolite para-aminobenzoic acid (PABA) to rescue ∆pabA/B and ∆aroC auxotrophy and enable cell growth. The Lossen substrate can also be synthesised from polyethylene terephthalate (PET) and applied to whole-cell biocatalytic reactions and fermentations generating industrial small molecule products – including the analgesic and antipyretic drug paracetamol – paving the way for a general strategy to addict E. coli and other industrial chassis strains to PET plastic waste as a bioremediation strategy and for the upcycling of plastic waste using engineered biology. Together, this work showcases how non-enzymatic biocompatible reactions can be interfaced and cooperate with microbial metabolism to expand the available toolbox of metabolic chemistry for small molecule synthesis in native and engineered cellular systems.