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Nat Chem Biol. 2018 Jun;14(6):556-564. doi: 10.1038/s41589-018-0052-1. Epub 2018 Apr 30.

Shared strategies for β-lactam catabolism in the soil microbiome.

Author information

1
Department of Pathology and Immunology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA.
2
The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA.
3
Wyss Institute for Biologically Inspired Engineering, Harvard, Cambridge, MA, USA.
4
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
5
US Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Aberdeen, MD, USA.
6
TMG Biosciences, LLC, Austin, TX, USA.
7
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
8
Department of Pathology and Immunology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA. dantas@wustl.edu.
9
The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA. dantas@wustl.edu.
10
Department of Molecular Microbiology, Washington University in St Louis School of Medicine, Saint Louis, MO, USA. dantas@wustl.edu.
11
Department of Biomedical Engineering, Washington University in St Louis, Saint Louis, MO, USA. dantas@wustl.edu.

Abstract

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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