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Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway

Author

Listed:
  • Chad W. Johnston

    (Massachusetts Institute of Technology)

  • Ahmed H. Badran

    (Broad Institute of MIT and Harvard)

  • James J. Collins

    (Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Harvard University
    Massachusetts Institute of Technology)

Abstract

Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing a mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs for expression in different organisms, potentially providing clues to improve heterologous expression of antibiotics. Here, we use phage-assisted continuous evolution (PACE) to achieve bioactivity-dependent adaptation of the BGC for the antibiotic bicyclomycin (BCM), facilitating improved production in a heterologous host. This proof-of-principle study demonstrates that features of natural bioactivity-dependent evolution can be engineered to access unforeseen routes of improving metabolic pathways and product yields.

Suggested Citation

  • Chad W. Johnston & Ahmed H. Badran & James J. Collins, 2020. "Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18018-2
    DOI: 10.1038/s41467-020-18018-2
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    Cited by:

    1. Mary S. Morrison & Tina Wang & Aditya Raguram & Colin Hemez & David R. Liu, 2021. "Disulfide-compatible phage-assisted continuous evolution in the periplasmic space," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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