RRC ID 35375
Author Sandoval NR, Mills TY, Zhang M, Gill RT.
Title Elucidating acetate tolerance in E. coli using a genome-wide approach.
Journal Metab. Eng.
Abstract Engineering organisms for improved performance using lignocellulose feedstocks is an important step towards a sustainable fuel and chemical industry. Cellulosic feedstocks contain carbon and energy in the form of cellulosic and hemicellulosic sugars that are not metabolized by most industrial microorganisms. Pretreatment processes that hydrolyze these polysaccharides often also result in the accumulation of growth inhibitory compounds, such as acetate and furfural among others. Here, we have applied a recently reported strategy for engineering tolerance towards the goal of increasing Escherichia coli growth in the presence of elevated acetate concentrations (Lynch et al., 2007). We performed growth selections upon an E. coli genome library developed using a moderate selection pressure to identify genomic regions implicated in acetate toxicity and tolerance. These studies identified a range of high-fitness genes that are normally involved in membrane and extracellular processes, are key regulated steps in pathways, and are involved in pathways that yield specific amino acids and nucleotides. Supplementation of the products and metabolically related metabolites of these pathways significantly increased growth rate (a 130% increase in specific growth) at inhibitory acetate concentrations. Our results suggest that acetate tolerance will not involve engineering of a single pathway; rather we observe a range of potential mechanisms for overcoming acetate based inhibition.
Volume 13(2)
Pages 214-24
Published 2011-3
DOI 10.1016/j.ymben.2010.12.001
PII S1096-7176(10)00105-9
PMID 21163359
MeSH Acetates / toxicity* Biofuels Cellulose / metabolism Escherichia coli / drug effects* Escherichia coli / genetics* Escherichia coli / growth & development Genetic Engineering* Genetic Fitness Genomics Metabolic Networks and Pathways / genetics*
IF 7.674
Times Cited 30
Prokaryotes E. coli NA