Lignin to adipic acid in a high-yield chemical and biological redox process (original) (raw)

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.

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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

Author notes

  1. These authors contributed equally: Kathryn M. Mains, Chad T. Palumbo, Davide Rigo, Matthew S. Webber

Authors and Affiliations

  1. Renewable Resources and Enabling Sciences Center, National Laboratory of the Rockies, Golden, CO, USA
    Kathryn M. Mains, Chad T. Palumbo, Davide Rigo, Matthew S. Webber, Gloria Rosetto, Si Tong Bao, Nicolette R. Meyer, Alexander F. Benson, Brett A. Boyle, Stefan J. Haugen, Morgan A. Ingraham, Logan C. Myers, Kelsey J. Ramirez, Kevin P. Sullivan, Davinia Salvachúa, Allison Z. Werner & Gregg T. Beckham
  2. Center for Bioenergy Innovation, Oak Ridge National Laboratory, Oak Ridge, TN, USA
    Kathryn M. Mains, Davide Rigo, Matthew S. Webber, Austin L. Carroll, William G. Alexander, Adam M. Guss, Allison Z. Werner & Gregg T. Beckham
  3. Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
    Austin L. Carroll, William G. Alexander, Miriam Silberman & Adam M. Guss
  4. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    Yuriy Román-Leshkov
  5. Department of Chemistry and Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI, USA
    Shannon S. Stahl

Authors

  1. Kathryn M. Mains
  2. Chad T. Palumbo
  3. Davide Rigo
  4. Matthew S. Webber
  5. Gloria Rosetto
  6. Si Tong Bao
  7. Austin L. Carroll
  8. Nicolette R. Meyer
  9. Alexander F. Benson
  10. Brett A. Boyle
  11. Stefan J. Haugen
  12. Morgan A. Ingraham
  13. William G. Alexander
  14. Miriam Silberman
  15. Logan C. Myers
  16. Kelsey J. Ramirez
  17. Kevin P. Sullivan
  18. Adam M. Guss
  19. Davinia Salvachúa
  20. Yuriy Román-Leshkov
  21. Shannon S. Stahl
  22. Allison Z. Werner
  23. Gregg T. Beckham

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

Correspondence toShannon S. Stahl, Allison Z. Werner or Gregg T. Beckham.

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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).

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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).

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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

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