4.8 Article

Shared strategies for β-lactam catabolism in the soil microbiome

Journal

NATURE CHEMICAL BIOLOGY
Volume 14, Issue 6, Pages 556-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41589-018-0052-1

Keywords

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Funding

  1. Edward Mallinckrodt, Jr. Foundation
  2. NIH Director's New Innovator Award
  3. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  4. National Institute of General Medical Sciences (NIGMS)
  5. National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [DP2DK098089, R01GM099538, R01AI123394]
  6. National Institute of Diabetes and Digestive and Kidney Diseases Training Grant [T32 DK077653]
  7. National Institute of Child Health and Development Training Grant [T32 HD049305]
  8. NHGRI Genome Analysis Training Program [T32 HG000045]
  9. NIGMS Cellular and Molecular Biology Training Program [T32 GM007067]
  10. NSF [DGE-1143954]
  11. Transformational Medical Technologies Initiative of the Defense Threat Reduction Agency, US Department of Defense
  12. Lundbeck Foundation [R140-2013-13496] Funding Source: researchfish
  13. NNF Center for Biosustainability [Bacterial Synthetic Biology] Funding Source: researchfish
  14. Novo Nordisk Fonden [NNF14OC0011335, NNF10CC1016517, NNF17OC0028232] Funding Source: researchfish

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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 beta-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 beta-lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a beta-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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