Lignin to adipic acid in a high-yield chemical and biological redox process

Abstract Viable manufacturing pathways to produce bio-based chemicals from renewable feedstocks, such as lignin derived from plant biomass, are needed to decarbonize the chemicals manufacturing sector. Converting the recalcitrant lignin polymer to valuable bioproducts remains a longstanding challenge in biorefining, with the highest reported single-product yield from lignin currently around 20 wt% (refs. 1,2,3,4). Most existing lignin depolymerization strategies target aryl–ether bond cleavage, which can produce aromatic monomers in yields of only about 30 wt%, and still as complex mixtures with C–C-linked dimers and oligomers5,6. The recalcitrance of these C–C linkages between aromatic moieties fundamentally limits single-product yields from lignin, prompting the development of strategies to efficiently cleave these C–C bonds3,7,8,9. Here we show how reductive processing of lignin from poplar accesses a hydrocarbon mixture of alkyl-aromatic monomers and oligomers that is privileged for oxidative conversion to monomeric aromatic carboxylic acids, comprising mostly benzoic acid and phthalic acid isomers in up to 73 wt% monomer yields, using a Co/Mn/Br catalyst. The soil bacterium Pseudomonas putida KT2440 was engineered to convert this mixture of aromatic carboxylic acids to muconolactone, a precursor to bio-based nylons, enabling final adipic acid yields up to 26 wt% (gram adipic acid per gram lignin) with a maximum theoretical yield of 57 wt%. This pairing of reductive and oxidative steps with lignin resembles processes in petrochemical refining and shows how lignin may be converted into a single, valuable bioproduct in high yields. This is a preview of subscription content, access via your institution Access options Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription £17.99 / 30 days cancel any time Subscribe to this journal Receive 52 print issues and online access £199.00 per year only £3.83 per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. £ 29.95 Prices may be subject to local taxes which are calculated during checkout Data availability Sequence data for environmental isolates and adaptive laboratory evolution populations and isolates are available on NCBI BioProject PRJNA1289884 (BioSample information listed in Supplementary Data 1). All other data from this study are included in the main text, Supplementary Information and Supplementary Data 1. References Liao, Y. et al. A sustainable wood biorefinery for low-carbon footprint chemicals production. Science 367, 1385–1390 (2020). Meng, Q. et al. Sustainable production of benzene from lignin. Nat. Commun. 12, 4534 (2021). Subbotina, E. et al. Oxidative cleavage of C–C bonds in lignin. Nat. Chem. 13, 1118–1125 (2021). Werner, A. Z. et al. Lignin conversion to β-ketoadipic acid by Pseudomonas putida via metabolic engineering and bioprocess development. Sci. Adv. 9, eadj0053 (2023). Schutyser, W. et al. Chemicals from lignin: an interplay of lignocellulose fractionation, depolymerisation, and upgrading. Chem. Soc. Rev. 47, 852–908 (2018). Questell-Santiago, Y. M., Galkin, M. V., Barta, K. & Luterbacher, J. S. Stabilization strategies in biomass depolymerization using chemical functionalization. Nat. Rev. Chem. 4, 311–330 (2020). Gu, N. X. et al. Autoxidation catalysis for carbon–carbon bond cleavage in lignin. ACS Cent. Sci. 9, 2277–2285 (2023). Palumbo, C. T. et al. Catalytic carbon–carbon bond cleavage in lignin via manganese–zirconium-mediated autoxidation. Nat. Commun. 15, 862 (2024). Palumbo, C. T. et al. Accessing monomers from lignin through carbon–carbon bond cleavage. Nat. Rev. Chem. 8, 799–816 (2024). Tomás, R. A. F., Bordado, J. C. M. & Gomes, J. F. P. p-Xylene oxidation to terephthalic acid: a literature review oriented toward process optimization and development. Chem. Rev. 113, 7421–7469 (2013). Speight, J. Petroleum refinery processes. In Kirk-Othmer Encyclopedia of Chemical Technology (Wiley, 2018); https://doi.org/10.1002/0471238961.1805060919160509.a01.pub3. Musser, M. T. Cyclohexanol and cyclohexanone. In Ullmann’s Encyclopedia of Industrial Chemistry (Wiley, 2000); https://doi.org/10.1002/14356007.a08_217 Zakzeski, J., Bruijnincx, P. C. A., Jongerius, A. L. & Weckhuysen, B. M. The catalytic valorization of lignin for the production of renewable chemicals. Chem. Rev. 110, 3552–3599 (2010). Sun, Z., Fridrich, B., de Santi, A., Elangovan, S. & Barta, K. Bright side of lignin depolymerization: toward new platform chemicals. Chem. Rev. 118, 614–678 (2018). Ralph, J., Lapierre, C. & Boerjan, W. Lignin structure and its engineering. Curr. Opin. Biotechnol. 56, 240–249 (2019). Lucarini, M. & Pedulli, G. F. Free radical intermediates in the inhibition of the autoxidation reaction. Chem. Soc. Rev. 39, 2106–2119 (2010). Stone, M. L. et al. Continuous hydrodeoxygenation of lignin to jet-range aromatic hydrocarbons. Joule 6, 2324–2337 (2022). Webber, M. S. et al. Lignin deoxygenation for the production of sustainable aviation fuel blendstocks. Nat. Mater. 23, 1622–1638 (2024). Webber, M. S. et al. Drop-in sustainable aviation fuels enabled by feedstock-agnostic lignin deoxygenation. Cell Rep. Phys. Sci. 6, 102687 (2025). Shanks, B. H. & Keeling, P. L. Bioprivileged molecules: creating value from biomass. Green Chem. 19, 3177–3185 (2017). Cywar, R. M., Rorrer, N. A., Hoyt, C. B., Beckham, G. T. & Chen, E. Y. X. Bio-based polymers with performance-advantaged properties. Nat. Rev. Mater. 7, 83–103 (2021). Partenheimer, W. Methodology and scope of metal/bromide autoxidation of hydrocarbons. Catal. Today 23, 69–158 (1995). Partenheimer, W. The aerobic oxidative cleavage of lignin to produce hydroxyaromatic benzaldehydes and carboxylic acids via metal/bromide catalysts in acetic acid/water mixtures. Adv. Synth. Catal. 351, 456–466 (2009). Liu, A. et al. Biomanufacturing of value-added chemicals from lignin. Curr. Opin. Biotechnol. 89, 103178 (2024). Pereyra-Camacho, M. A. & Pardo, I. Biological degradation of phthalates: from bioremediation to plastic waste valorization. ChemSusChem 19, e202501955 (2026). Weimer, A., Kohlstedt, M., Volke, D. C., Nikel, P. I. & Wittmann, C. Industrial biotechnology of Pseudomonas putida: advances and prospects. Appl. Microbiol. Biotechnol. 104, 7745–7766 (2020). Martínez-García, E. & de Lorenzo, V. Pseudomonas putida as a synthetic biology chassis and a metabolic engineering platform. Curr. Opin. Biotechnol. 85, 103025 (2024). Abu-Omar, M. M. et al. Guidelines for performing lignin-first biorefining. Energy Environ. Sci. 14, 262–292 (2021). Dao Thi, H. et al. Identification and quantification of lignin monomers and oligomers from reductive catalytic fractionation of pine wood with GC × GC – FID/MS. Green Chem. 24, 191–206 (2022). Sullivan, M. M., Chen, C.-J. & Bhan, A. Catalytic deoxygenation on transition metal carbide catalysts. Catal. Sci. Technol. 6, 602–616 (2016). Gong, W. H. In Industrial Arene Chemistry (ed. Mortier, J.) 1107–1135 (Wiley, 2023). Weeda, E. P. et al. O2-permeable membrane reactor for continuous oxidative depolymerization of lignin. Joule 8, 3336–3346 (2024). Jiménez, J. I., Miñambres, B., García, J. L. & Díaz, E. Genomic analysis of the aromatic catabolic pathways from Pseudomonas putida KT2440. Environ. Microbiol. 4, 824–841 (2002). Fuchs, G., Boll, M. & Heider, J. Microbial degradation of aromatic compounds—from one strategy to four. Nat. Rev. Microbiol. 9, 803–816 (2011). Werner, A. Z. et al. Tandem chemical deconstruction and biological upcycling of poly(ethylene terephthalate) to β-ketoadipic acid by Pseudomonas putida KT2440. Metab. Eng. 67, 250–261 (2021). Sullivan, K. P. et al. Mixed plastics waste valorization through tandem chemical oxidation and biological funneling. Science 378, 207–211 (2022). Huenemann, J. D. et al. Combinatorial pathway engineering using multiplex serine recombinase-assisted genome engineering (mSAGE). Preprint at bioRxiv https://doi.org/10.1101/2025.07.11.664204 (2025). Boll, M., Geiger, R., Junghare, M. & Schink, B. Microbial degradation of phthalates: biochemistry and environmental implications. Environ. Microbiol. Rep. 12, 3–15 (2019). Elmore, J. R. et al. High-throughput genetic engineering of nonmodel and undomesticated bacteria via iterative site-specific genome integration. Sci. Adv. 9, eade1285 (2023). Nomura, Y., Harashima, S. & Oshima, Y. PHT, a transmissible plasmid responsible for phthalate utilization in Pseudomonas putida. J. Ferment. Bioeng. 70, 295–300 (1990). Shimodaira, J. et al. Draft genome sequence of Comamonas sp. strain E6 (NBRC 107749), a degrader of phthalate isomers through the protocatechuate 4,5-cleavage pathway. Genome Announc. 3, e0064315 (2015). Sandberg, T. E., Salazar, M. J., Weng, L. L., Palsson, B. O. & Feist, A. M. The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology. Metab. Eng. 56, 1–16 (2019). Johnson, C. W. et al. Innovative chemicals and materials from bacterial aromatic catabolic pathways. Joule 3, 1523–1537 (2019). Rorrer, N. A. et al. Production of β-ketoadipic acid from glucose in Pseudomonas putida KT2440 for use in performance-advantaged nylons. Cell Rep. Phys. Sci. 3, 100840 (2022). Vardon, D. R. et al. cis,cis-Muconic acid: separation and catalysis to bio-adipic acid for nylon-6,6 polymerization. Green Chem. 18, 3397–3413 (2016). Capelli, S. et al. Bio-adipic acid production by catalysed hydrogenation of muconic acid in mild operating conditions. Appl. Catal. B 218, 220–229 (2017). Capelli, S. et al. Bio adipic acid production from sodium muconate and muconic acid: a comparison of two systems. ChemCatChem 11, 3075–3084 (2019). Khalil, I., Quintens, G., Junkers, T. & Dusselier, M. Muconic acid isomers as platform chemicals and monomers in the biobased economy. Green Chem. 22, 1517–1541 (2020). Wilkes, R. A. et al. Comparison of microbial strains as candidate hosts and genetic reservoirs for the valorization of lignin streams. Green Chem. 26, 12053–12069 (2024). Worsey, M. J. & Williams, P. A. Metabolism of toluene and xylenes by Pseudomonas (putida (arvilla) mt-2: evidence for a new function of the TOL plasmid. J. Bacteriol. 124, 7–13 (1975). Carraher, J. M., Pfennig, T., Rao, R. G., Shanks, B. H. & Tessonnier, J.-P. cis,cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C6-1,4-diacid monomers. Green Chem. 19, 3042–3050 (2017). Ver Elst, C. et al. Synthesis of levulinic acids from muconic acids in hot water. Angew. Chem. Int. Ed. 62, e202309597 (2023). Bartling, A. W. et al. Techno-economic analysis and life cycle assessment of a biorefinery utilizing reductive catalytic fractionation. Energy Environ. Sci. 14, 4147–4168 (2021). Arts, W. et al. Stepping away from purified solvents in reductive catalytic fractionation: a step forward towards a disruptive wood biorefinery process. Energy Environ. Sci. 16, 2518–2539 (2023). Lee, S. Y. et al. A comprehensive metabolic map for production of bio-based chemicals. Nat. Catal. 2, 18–33 (2019). Sluiter, A. et al. NREL/TP-510-42618: Determination of Structural Carbohydrates and Lignin in Biomass (National Renewable Energy Laboratory, 2008). Miscall, J., Christensen, E. D., Olstad, J., Deutch, S. & Ferrell, J. R. III NREL/TP-5100-80967: Determination of Carbon, Hydrogen, Nitrogen, and Oxygen in Bio-oils (National Renewable Energy Laboratory, 2021). Woodworth, S. P., Ramirez, K. J. & Beckham, G. T. Aromatic monomers analysis for reductive catalytic fractionation of lignin by liquid chromatography with diode array detection. protocols.io https://doi.org/10.17504/protocols.io.bp2l6x6jdlqe/v1 (2025). Haugen, S., Alt, H., Ramirez, K., Michener, W. E. & Beckham, G. T. Analysis of HDO autoxidation products by UHPLC-DAD. protocols.io https://doi.org/10.17504/protocols.io.kqdg31ex1l25/v1 (2026). Hosseini-Sarvari, M., Ataee-Kachouei, T. & Moeini, F. Preparation, characterization, and catalytic application of nano Ag/ZnO in the oxidation of benzylic C–H bonds in sustainable media. RSC Adv. 5, 9050–9056 (2015). Gomez, M. V. & de la Hoz, A. NMR reaction monitoring in flow synthesis. Beilstein J. Org. Chem. 13, 285–300 (2017). Wang, Z. et al. Cooperative interplay between a flexible PNN–Ru(II) complex and a NaBH4 additive in the efficient catalytic hydrogenation of esters. Catal. Sci. Technol. 7, 1297–1304 (2017). Zhang, Y. et al. Catalyst-free aerobic oxidation of aldehydes into acids in water under mild conditions. Green Chem. 19, 5708–5713 (2017). Wu, D. H., Chen, A. D. & Johnson, C. S. An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses. J. Magn. Reson. A 115, 260–264 (1995). Stanley, L., Katahira, R. & Beckham, G. T. Molecular weight determination of lignin via gel permeation chromatography. protocols.io https://doi.org/10.17504/protocols.io.n2bvj1r15vk5/v1 (2026). Wick, R. R. et al. Trycycler: consensus long-read assemblies for bacterial genomes. Genome Biol. 22, 266 (2021). Kolmogorov, M., Yuan, J., Lin, Y. & Pevzner, P. A. Assembly of long, error-prone reads using repeat graphs. Nat. Biotechnol. 37, 540–546 (2019). Vaser, R. & Šikić, M. Time- and memory-efficient genome assembly with Raven. Nat. Comput. Sci. 1, 332–336 (2021). Li, H. Minimap and miniasm: fast mapping and de novo assembly for noisy long sequences. Bioinformatics 32, 2103–2110 (2016). Kasai, D. et al. 2,3-Dihydroxybenzoate meta-cleavage pathway is involved in o-phthalate utilization in Pseudomonas sp. strain PTH10. Sci. Rep. 9, 1253 (2019). Farasat, I. et al. Efficient search, mapping, and optimization of multi-protein genetic systems in diverse bacteria. Mol. Syst. Biol. 10, 731 (2014). Halper, S. M., Hossain, A. & Salis, H. M. Synthesis success calculator: predicting the rapid synthesis of DNA fragments with machine learning. ACS Synth. Biol. 9, 1563–1571 (2020). Reis, A. C. & Salis, H. M. An automated model test system for systematic development and improvement of gene expression models. ACS Synth. Biol. 9, 3145–3156 (2020). Cetnar, D. P. & Salis, H. M. Systematic quantification of sequence and structural determinants controlling mRNA stability in bacterial operons. ACS Synth. Biol. 10, 318–332 (2021). Elmore, J. R., Furches, A., Wolff, G. N., Gorday, K. & Guss, A. M. Development of a high efficiency integration system and promoter library for rapid modification of Pseudomonas putida KT2440. Metab. Eng. Commun. 5, 1–8 (2017). Johnson, C. W. & Beckham, G. T. Aromatic catabolic pathway selection for optimal production of pyruvate and lactate from lignin. Metab. Eng. 28, 240–247 (2015). Salvachúa, D. et al. Bioprocess development for muconic acid production from aromatic compounds and lignin. Green Chem. 20, 5007–5019 (2018). Ramirez, K., Ingraham, M., Haugen, S. & Beckham, G. T. Analysis of a lignin derived single product using chemical and biological redox using UHPLC-MS/MS-DAD. protocols.io https://doi.org/10.17504/protocols.io.36wgqprjyvk5/v1 (2026). Alt, H. M. et al. Analysis of sugars, small organic acids, and alcohols by HPLC-RID. protocols.io https://doi.org/10.17504/protocols.io.5qpvob7y9l4o/v2 (2024). Acknowledgements We thank M. L. Stone for a critical review of the paper and S. Lask for assistance in product quantification. Funding This work was authored in part by the National Laboratory of the Rockies for the US Department of Energy (DOE) under contract number DE-AC36-08GO28308. This work was authored in part by Oak Ridge National Laboratory, which is managed by UT-Battelle, LLC, for the US DOE under contract DE-AC05-00OR22725. Funding to K.M.M., C.T.P., M.S.W., G.R., S.T.B., A.F.B., B.A.B., S.J.H., M.A.I., N.R.M., L.C.M., K.J.R., K.P.S., D.S., Y.R.-L., A.Z.W. and G.T.B. was provided by the US DOE Office of Critical Minerals and Energy Innovation Alternative Fuels and Feedstocks Office. For K.M.M., D.R., M.S.W., A.L.C., A.M.G., Y.R.-.L., A.Z.W. and G.T.B., this material is also based upon work at the Center for Bioenergy Innovation supported by the US Department of Energy, Office of Science, Biological and Environmental Research under contract number ERKP886. Contributions by S.S.S. were supported by the US Department of Energy, Office of Basic Energy Sciences, under award number DE-FG02-05ER15690. The views expressed in the article do not necessarily represent the views of the DOE or the US Government. The US Government retains and the publisher, by accepting the article for publication, acknowledges that the US Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for US Government purposes. Author information Authors and Affiliations Contributions Conceptualization: K.P.S., S.S.S., A.Z.W. and G.T.B. Methodology: K.M.M., C.T.P., D.R., M.S.W., G.R., A.L.C., N.R.M., K.J.R., K.P.S., A.M.G., D.S., Y.R.-L., S.S.S., A.Z.W. and G.T.B. Investigation: K.M.M., C.T.P., D.R., M.S.W., G.R., S.T.B., A.L.C., N.R.M., A.F.B, B.A.B., S.J.H., M.A.I., W.G.A., M.S., L.C.M., K.J.R. and A.Z.W. M.S.W. and L.C.M. performed the RCF reactions. M.S.W. performed the HDO reactions. C.T.P., D.R., M.S.W. and S.T.B. performed the autoxidation reactions. A.L.C. performed the phthalate catabolism bioprospecting. A.L.C, W.G.A. and M.S. genome-sequenced the phthalate-catabolizing bacterial isolates in this work. K.M.M., A.L.C., M.S. and A.Z.W. engineered the bacterial strains in this study. K.M.M. and A.L.C. performed small-scale bacterial cultivations and adaptive laboratory evolution. N.R.M. performed the bioreactor experiments. G.R. and B.A.B. performed conversion of muconolactone to adipic acid and dimethyl β-ketoadipic acid. A.F.B., S.J.H., M.A.I. and K.J.R. developed and performed analytical measurements. Visualization: K.M.M., C.T.P., D.R., M.S.W. and A.Z.W. Funding acquisition: A.M.G., D.S., Y.R.-L., S.S.S., A.Z.W. and G.T.B. Supervision: A.M.G., D.S., Y.R.-L., S.S.S., A.Z.W. and G.T.B. Writing—original draft: K.M.M., C.T.P., D.R., M.S.W., G.R., A.L.C., N.R.M., K.J.R., S.S.S, A.Z.W. and G.T.B. Writing—review and editing: all authors reviewed and approved the paper. Corresponding authors Ethics declarations Competing interests K.M.M., C.T.P., A.L.C., K.P.S., A.M.G., Y.R.-L., S.S.S., A.Z.W. and G.T.B. have filed a patent application on this concept (US provisional patent no U.S. 2024/0327877 A1). Peer review Peer review information Nature thanks Micaela Chacόn, Neil Dixon and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Additional information Extended data figures and tables Extended Data Fig. 1 Sankey diagrams showing the actual (a) and theoretical (b) mass yields of products through the overall process. (a) Mass yields were evaluated either gravimetrically or via analytical methods through the whole process as described in the experimental procedures section. Relevant assumptions have been detailed in the Supplementary text and Extended Data Fig. 2, while numerical values can be found in Data S1. (b) Calculation of theoretical process yields was performed as described in the Supplementary text. Calculations can be found in Data S1. Reaction conditions for RCF: 3 g poplar, 300 mg 5 wt% Ru/C, 30 mL MeOH/H2O (2/1 v/v), 30 bar H2, 225 °C, 700 rpm stirring, 3 h reaction time (not including ~30 min heat-up). Reaction conditions for HDO: poplar lignin RCF oil as the substrate, 8.6 g Mo2C (60–100 mesh), 0.3 mL/min lignin oil, 270 mL/min H2, 62 bar, 350 °C (first pass), 375 °C (second pass), and toluene at 3 mL/min for 30 min during start-up. Reaction conditions for autoxidation: 500 mg HDO lignin oil, 20 mL AcOH, 25 mg (5 wt%) Co(OAc)2•4H2O, 25 mg (5 wt%) Mn(OAc)2•4H2O, and 5 mg (1 wt%) NaBr (added from AcOH stock solutions of dissolved catalysts), 6 bar O2, 220 °C, 3 h reaction not including heat-up time of ~0.5 h. Reaction conditions for bioconversion: KMM037 was cultivated in shake flasks (30 °C, 225 rpm) with 20 mM glucose and 10 mM aromatics from autoxidation substrate. Reaction conditions for muconolactone to adipic acid: 3 g muconolactone, 15 wt% Amberlyst-15, 50 mL MeOH, 68 °C, 16 h; 0.5 g muconolactone methyl ester, 1 equiv K2CO3, H2O, RT, 16 h; 5 bar H2, 50 mg Pd/C (5 wt% loading), H2O, 22 °C, 3 h; 1 equiv K2CO3, H2O, 70 °C. Extended Data Fig. 2 Summary of yield equations used in determining stepwise process yields used to determine overall process yields reported in Fig. 1 and Extended Data Fig. 1. A more detailed explanation of yield calculations and assumptions can be found in the Supplementary text and Data S1. Abbreviations: RCF, reductive catalytic fractionation; HDO, hydrodeoxygenation; AO, autoxidation; BF, biological funneling; HYD, hydrogenation; Me, methyl; Y, yield; stoic, stoichiometric; theo, theoretical; sub, substrate. Figure created in BioRender; Mains, K. https://BioRender.com/9hcf8sw (2026). Supplementary information Supplementary Information (download PDF ) This file contains Supplementary Text, Materials, Figs. 1–66, Tables 1–7 and References. Supplementary Data 1 (download XLSX ) This file includes the source data for Figs. 2–4, source data for Supplementary Figs. 1, 2, 5, 9 and 11, and yield calculations. It also contains protein sequence alignment information and Bioproject information for sequences collected in this work. Rights and permissions About this article Cite this article Mains, K.M., Palumbo, C.T., Rigo, D. et al. Lignin to adipic acid in a high-yield chemical and biological redox process. Nature (2026). https://doi.org/10.1038/s41586-026-10580-x Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1038/s41586-026-10580-x