E. coli are poised to grow using 5'-deoxynucleosides via MtnR and CRP regulation of DHAP shunt gene expression
The dihydroxyacetone phosphate (DHAP) shunt is a multifunctional pathway for the metabolism of 5'-deoxynucleosides and 5-deoxypentose sugars, such as 5'-methylthioadenosine (MTA) and 5'-deoxyadenosine (5dAdo), into DHAP and an aldehyde species depending on the substrate. Previous work revealed that E. coli strains with the DHAP shunt can utilize exogenous MTA, 5dAdo, and derivatives thereof as sole carbon and energy sources for growth. However, if and how the DHAP shunt was regulated for 5-deoxynucleoside and 5-deoxypentose sugar metabolism remained unknown. In the present work, the DHAP shunt genes (mtnK, mtnA, ald2) and a putative transporter gene of E. coli ATCC 25922 are observed to form an operon, which can be expressed from two separate transcription start sites (TSSs). The distal, low-activity TSS appears to be constitutive, while the proximal primary TSS is regulated based on the identity of available growth substrates by at least two transcriptional regulators. First YjhU, a DeoR family regulator previously of unknown function that we designate as MtnR, functions as a repressor of the DHAP shunt operon when DHAP shunt substrates are absent. Further, the cyclic AMP receptor protein (CRP) imposes carbon catabolite repression while glucose is available. Based on comparative sequence analysis, the E. coli DHAP shunt promoter region is highly conserved, including strains of the globally disseminated ST131 lineage of Extraintestinal Pathogenic E. coli, indicating a similar regulatory paradigm. Thus the E. coli DHAP shunt is a previously unrecognized pathway for use of 5-deoxynucleosides and 5-deoxypentose sugars as alternative carbon sources when glucose is scarce. Overall design: RNA-Seq analysis of wild-type E. coli versus DmtnR strains