Carbon-negative biosynthesis of pyrone and pyridine dicarboxylic acids from terephthalic acid via continuous mixotrophic gas fermentation in Cupriavidus necator H16

Waters, E.; Conradie, A.; Bommareddy, R. R.

doi:10.64898/2026.03.12.709797

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bioRxiv · 10.64898/2026.03.12.709797

Carbon-negative biosynthesis of pyrone and pyridine dicarboxylic acids from terephthalic acid via continuous mixotrophic gas fermentation in Cupriavidus necator H16

Waters, E.·Conradie, A.·Bommareddy, R. R.

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Abstract

Industrial defossilisation requires carbon-negative routes for sustainable chemical production. Bioprocesses based on renewable feedstocks are often constrained by biogenic CO2 emissions, reducing yields and undermining environmental performance. Here, we report a mixotrophic gas fermentation strategy using the chemolithoautotroph Cupriavidus necator H16 that simultaneously assimilates CO2 for cell growth and biocatalyst generation while converting the PET monomer terephthalic acid (TPA) into value-added biopolymer precursors. This process achieved complete conversion of TPA to 2-pyrone-4,6-dicarboxylic acid (PDC) with titres of 24.5 g/L and a productivity of 0.47 g/L{middle dot}h. Conversion to pyridine dicarboxylic acids (2,4- and 2,5-PDCA) was less efficient ([~]22% and [~]4% respectively) due to metabolic limitations such as intermediate toxicity, pH and ammonia-dependent spontaneous cyclisation. Our results establish the first carbon-negative route coupling simultaneous CO2 assimilation with plastic monomer valorisation, providing a blueprint for sustainable biomanufacturing aligned with global climate and circular economy goals.

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Waters, E., Conradie, A., Bommareddy, R. R.. 2026-03-16. Carbon-negative biosynthesis of pyrone and pyridine dicarboxylic acids from terephthalic acid via continuous mixotrophic gas fermentation in Cupriavidus necator H16. https://doi.org/10.64898/2026.03.12.709797

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