Abstract:
:A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory functions of the lost gene. The pgi gene, whose product catalyzes the second step in glycolysis, was deleted in a growth-optimized Escherichia coli K-12 MG1655 strain. The initial knockout (KO) strain exhibited an 80% drop in growth rate that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi-omic data sets showed that the loss of pgi substantially shifted pathway usage, leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.IMPORTANCE A mechanistic understanding of how microbes are able to overcome the loss of a gene through regulatory and metabolic changes is not well understood. Eight independent adaptive laboratory evolution (ALE) experiments with pgi knockout strains resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.
journal_name
Appl Environ Microbioljournal_title
Applied and environmental microbiologyauthors
McCloskey D,Xu S,Sandberg TE,Brunk E,Hefner Y,Szubin R,Feist AM,Palsson BOdoi
10.1128/AEM.00823-18subject
Has Abstractpub_date
2018-09-17 00:00:00issue
19eissn
0099-2240issn
1098-5336pii
AEM.00823-18journal_volume
84pub_type
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