Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Johnston CW,Badran AH,Collins JJ

doi

10.1038/s41467-020-18018-2

subject

Has Abstract

pub_date

2020-08-21 00:00:00

pages

4202

issue

1

issn

2041-1723

pii

10.1038/s41467-020-18018-2

journal_volume

11

pub_type

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