Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway

Chad W. Johnston, Ahmed H. Badran and James J. Collins ()
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Chad W. Johnston: Massachusetts Institute of Technology
Ahmed H. Badran: Broad Institute of MIT and Harvard
James J. Collins: Massachusetts Institute of Technology

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18018-2

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DOI: 10.1038/s41467-020-18018-2

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