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Table 1 Rational, semi-rational and random approaches in strain engineering

From: A metabolomics-based strategy for identification of gene targets for phenotype improvement and its application to 1-butanol tolerance in Saccharomyces cerevisiae

Rational

Semi-rational

Random

Gene modifications based on knowledge of genetic mechanisms and metabolic pathways governing the phenotype

Genetic modifications based on system-level comparison between strains, conditions, etc.

Genetic changes driven by random processes

Ex. Expression of heat-shock proteins or alcohol efflux pumps for heat or alcohol stress tolerance, respectively

Ex. Genome-wide or transcriptome-wide comparison

Ex. Laboratory evolution, induced transcription factor mutagenesis

Dependence on availability of prior knowledge

Not limited by lack of prior knowledge

Not limited by lack of prior knowledge

Results contribute additional information on relevant or important genes

Results contribute additional information on relevant or important genes

Results by themselves do not provide information on which genes are relevant/important

Elucidation of mechanisms is complicated and time-consuming

High-throughput, comprehensive ‘omics’ analytical technology is required

Screening step often required to recover the improved strains