Escherichia coli primarily constitutes 0.1–5% of the mammalian gut microbiome and can also be found in the gut of birds, reptiles, and fish, as well as in soil, water, and plants [1]. This facultative anaerobe experiences various environments and employs sophisticated mechanisms to respond to fluctuating levels of nutrients between feast and famine. Throughout the small intestine, amino acids are exceedingly abundant [2], and E. coli imports and catabolizes several amino acids as nitrogen sources and occasionally as carbon and energy sources 3, 4. In contrast, the mammalian large intestine is condensed with gut microbiota and is thought to be limiting for amino acids [5], which are degraded into ammonium and organic acids by the predominant Firmicutes species or utilized by amino acid auxotrophs [6].

E. coli is able to synthesize amino acids at the expense of energy, which depends on various carbon sources and precursor compounds 7, 8, 9. Primarily, E. coli assimilates ammonium into the common carbon skeleton, 2-oxoglutarate (OG), to yield glutamate and glutamine through two biosynthetic pathways [10]. The first pathway by glutamate dehydrogenase (GDH) produces glutamate without ATP consumption. In the second pathway, glutamine synthetase (GS) converts glutamate to glutamine using one molecule of ATP, and then glutamate synthase (GOGAT) transfers the amide group from glutamine to 2-OG, yielding two molecules of glutamate. Glutamate serves as the major donor of the amine group to keto acids to synthesize amino acids, while glutamine provides its amide group for several amino acids, nucleotides, and amino sugars. In addition, some other amino acids can serve as the amine sources for glutamate synthesis through recently discovered minor routes [11].

In response to nitrogen availability, the concentrations of glutamine and 2-OG exhibit rapid fluctuations through direct alterations in the enzyme activities, which accompanies regulation in the expression levels. The responses to the presence of amino acids, including transcriptional regulators and attenuators, have extensively been studied and fostered our knowledge of the regulation of gene expression in general. The network and regulation of central nitrogen metabolism in E. coli have been comprehensively reviewed in [12]. In this review, I will highlight recent advances and new aspects of the regulation at posttranslational, transcriptional, and posttranscriptional levels.