Title	Multiple optimal phenotypes overcome redox and glycolytic intermediate metabolite imbalances in knockout evolutions.
Year of Publication	2018
Authors	D. McCloskey; S. Xu; T.E. Sandberg; E. Brunk; Y. Hefner; R. Szubin; A.M. Feist; B.O. Palsson
Journal	PLoS Comput Biol
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 gene, whose product catalyzes the second step in glycolysis, was deleted in a growth optimized K-12 MG1655 strain. The initial knock-out (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 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 loss of a major gene product were revealed. 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 gene, whose product catalyzes the second step in glycolysis, was deleted in a growth optimized K-12 MG1655 strain. Eight independent adaptive laboratory evolution (ALE) experiments 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 loss of a major gene product were revealed.
PubMed ID	PubMed