title: Effects of genetic variation on the E. coli host-circuit interface.
abstract: Predictable operation of engineered biological circuitry requires the knowledge of host factors that compete or interfere with designed function. Here, we perform a detailed analysis of the interaction between constitutive expression from a test circuit and cell-growth properties in a subset of genetic variants of the bacterium Escherichia coli. Differences in generic cellular parameters such as ribosome availability and growth rate are the main determinants (89%) of strain-specific differences of circuit performance in laboratory-adapted strains but are responsible for only 35% of expression variation across 88 mutants of E. coli BW25113. In the latter strains, we identify specific cell functions, such as nitrogen metabolism, that directly modulate circuit behavior. Finally, we expose aspects of carbon metabolism that act in a strain- and sequence-specific manner. This method of dissecting interactions between host factors and heterologous circuits enables the discovery of mechanisms of interference necessary for the development of design principles for predictable cellular engineering.
authors.affiliation: Department of Bioengineering, University of California, 955 Energy Biosciences Building, 2151 Berkeley Way, Berkeley, CA 94704, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cardinale
authors.forename: Marcin Pawel
authors.initials: MP
authors.lastname: Joachimiak
authors.forename: Adam Paul
authors.initials: AP
authors.lastname: Arkin
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D014644:Genetic Variation; D054884:Host-Pathogen Interactions / Q000235:genetics