Enzyme promiscuity shapes evolutionary innovation and optimization

A computational model of underground metabolism and laboratory evolution experiments were employed to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in E. coli K-12 MG1655. After as few as 20 generations, the evolving populations repeatedly acquired the capacity to grow on five predicted novel substrates--D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate--none of which could support growth in wild-type cells. Promiscuous enzyme activities played key roles in multiple phases of adaptation. Potential mechanisms for optimizing growth on the non-native carbon sources were explored by analyzing the transcriptomes of initial and endpoint populations. RNAseq was performed on various evolved populations grown on four different carbon sources: D-lyxose, D-2-deoxyribose, D-arabinose, and m-tartrate. Differentially expressed genes were examined comparing endpoint (optimized) samples to initial (innovation) samples.