Finding targets for genome reduction in Streptomyces lividans TK24 using flux balance analysis

A genome reduction can be a good starting point for optimizing a wild-type strain for use in an industrial process. In a genome reduction, a selection of genes is removed with the intention of obtaining a robust strain with enhanced production properties. The complex soil bacterium Streptomyces lividans TK24 produces many compounds that can hinder the industrial objective. Genome reduction is often based on phylogenetic conservation and absolute gene expression. Here, flux balance analysis is proposed as an additional and complementary method for identifying potential targets for genome reduction. The effect of deletions of single metabolic genes and selected groups of adjacent metabolic genes on bacterial growth is simulated in a high throughput fashion. Targets identified through this method show lower gene expression and are less likely to be conserved between different Streptomyces strains. Gene expression data are used for assessing the effect of gene deletions in silico to improve prediction accuracy.