Adaptive laboratory evolution of a genome-reduced Escherichia coli

Donghui Choe, Jun Hyoung Lee, Minseob Yoo, Soonkyu Hwang, Bong Hyun Sung, Suhyung Cho, Bernhard Palsson, Sun Chang Kim () and Byung-Kwan Cho ()
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Donghui Choe: Korea Advanced Institute of Science and Technology
Jun Hyoung Lee: Korea Advanced Institute of Science and Technology
Minseob Yoo: Korea Advanced Institute of Science and Technology
Soonkyu Hwang: Korea Advanced Institute of Science and Technology
Bong Hyun Sung: Intelligent Synthetic Biology Center
Suhyung Cho: Korea Advanced Institute of Science and Technology
Bernhard Palsson: University of California San Diego
Sun Chang Kim: Korea Advanced Institute of Science and Technology
Byung-Kwan Cho: Korea Advanced Institute of Science and Technology

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Synthetic biology aims to design and construct bacterial genomes harboring the minimum number of genes required for self-replicable life. However, the genome-reduced bacteria often show impaired growth under laboratory conditions that cannot be understood based on the removed genes. The unexpected phenotypes highlight our limited understanding of bacterial genomes. Here, we deploy adaptive laboratory evolution (ALE) to re-optimize growth performance of a genome-reduced strain. The basis for suboptimal growth is the imbalanced metabolism that is rewired during ALE. The metabolic rewiring is globally orchestrated by mutations in rpoD altering promoter binding of RNA polymerase. Lastly, the evolved strain has no translational buffering capacity, enabling effective translation of abundant mRNAs. Multi-omic analysis of the evolved strain reveals transcriptome- and translatome-wide remodeling that orchestrate metabolism and growth. These results reveal that failure of prediction may not be associated with understanding individual genes, but rather from insufficient understanding of the strain’s systems biology.

Date: 2019
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DOI: 10.1038/s41467-019-08888-6

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