The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates. Genomic and transcriptomic sequencing revealed β-lactamase, amidase, and phenylacetic acid catabolon upregulation. Knocking out part of the phenylacetic acid catabolon or an apparent penicillin utilization operon (put) resulted in loss of penicillin catabolism in one isolate. A hydrolase from the put operon was found to degrade in vitro benzylpenicilloic acid, the β-lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a β-lactamase and a penicillin amidase or the put operon, enabling it to grow using penicillin or benzylpenicilloic acid, respectively. Elucidation of additional pathways may allow bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with industrial utility.

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This work is supported in part by awards to G.D. through the Edward Mallinckrodt, Jr. Foundation (Scholar Award), and from the NIH Director’s New Innovator Award (http://commonfund.nih.gov/newinnovator/), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK: http://www.niddk.nih.gov/), the National Institute of General Medical Sciences (NIGMS: http://www.nigms.nih.gov/), and the National Institute of Allergy and Infectious Diseases (NIAID: https://www.niaid.nih.gov/) of the National Institutes of Health (NIH) under award numbers DP2DK098089, R01GM099538, and R01AI123394, respectively. T.S.C. received support from a National Institute of Diabetes and Digestive and Kidney Diseases Training Grant through award number T32 DK077653 (P.I. Tarr, Principal Investigator) and a National Institute of Child Health and Development Training Grant through award number T32 HD049305 (K.H. Moley, Principal Investigator). K.J.F. received support from the NHGRI Genome Analysis Training Program (T32 HG000045), the NIGMS Cellular and Molecular Biology Training Program (T32 GM007067), and the NSF as a graduate research fellow (award number DGE-1143954). M.K.G. received support as a Mr. and Mrs. Spencer T. Olin Fellow at Washington University and from the NSF as a graduate research fellow (DGE-1143954). Sequencing through the US Army Edgewood Chemical Biological Center was supported in part through funding provided by the Transformational Medical Technologies Initiative of the Defense Threat Reduction Agency, US Department of Defense. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. We are thankful to J. Hoisington-Lopez in the Center for Genome Sciences and Systems Biology at Washington University in St. Louis School of Medicine for Illumina sequencing support, T. Wencewicz and B. Evans for their useful discussions regarding biochemistry and LC–MS and members of the Dantas lab for general helpful discussions regarding the manuscript.

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  1. Deceased.


  1. Department of Pathology and Immunology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA

    • Terence S. Crofts
    • , Bin Wang
    •  & Gautam Dantas
  2. The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA

    • Terence S. Crofts
    • , Bin Wang
    • , Aaron Spivak
    • , Kevin J. Forsberg
    • , Molly K. Gibson
    •  & Gautam Dantas
  3. Wyss Institute for Biologically Inspired Engineering, Harvard, Cambridge, MA, USA

    • Tara A. Gianoulis
  4. US Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Aberdeen, MD, USA

    • Lauren A. Johnsky
    • , Stacey M. Broomall
    • , C. Nicole Rosenzweig
    • , Evan W. Skowronski
    •  & Henry S. Gibbons
  5. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark

    • Morten O. A Sommer
  6. Department of Molecular Microbiology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA

    • Gautam Dantas
  7. Department of Biomedical Engineering, Washington University in St Louis, Saint Louis, MO, USA

    • Gautam Dantas
  8. Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, UK

    • Kevin J. Forsberg
  9. TMG Biosciences, LLC, Austin, TX, UK

    • Evan W. Skowronski


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T.S.C., A.S., T.A.G., M.O.A.S., and G.D. conceived of experiments and design of work. T.S.C., B.W., A.S., and T.A.G. performed in vitro, microbial, and transcriptomic experiments. L.A.J., S.M.B., C.N.R., E.W.S., and H.S.G. sequenced strain genomes. T.S.C., A.S., T.A.G., K.J.F, and M.K.G. provided analyses. Article drafting was performed by T.S.C. with critical revision performed by T.S.C., B.W., A.S., K.J.F, M.K.G., M.O.A.S., and G.D.

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The authors declare no competing interests.

Corresponding author

Correspondence to Gautam Dantas.

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  2. Reporting Summary

  3. Supplementary Dataset 1

    RNA-seq count dataset

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