The Distinctive Regulation of Cyanobacterial Glutamine Synthetase

Abstract

Glutamine synthetase (GS) features prominently in bacterial nitrogen assimilation as it catalyzes the entry of bioavailable nitrogen in form of ammonium into cellular metabolism. The classic example, the comprehensively characterized GS of enterobacteria, is subject to exquisite regulation at multiple levels, among them gene expression regulation to control GS abundance, as well as feedback inhibition and covalent modifications to control enzyme activity. Intriguingly, the GS of the ecologically important clade of cyanobacteria features fundamentally different regulatory systems to those of most prokaryotes. These include the interaction with small proteins, the so-called inactivating factors (IFs) that inhibit GS linearly with their abundance. In addition to this protein interaction-based regulation of GS activity, cyanobacteria use alternative elements to control the synthesis of GS and IFs at the transcriptional level. Moreover, cyanobacteria evolved unique RNA-based regulatory mechanisms such as glutamine riboswitches to tightly tune IF abundance. In this review, we aim to outline the current knowledge on the distinctive features of the cyanobacterial GS encompassing the overall control of its activity, sensing the nitrogen status, transcriptional and post-transcriptional regulation, as well as strain-specific differences.

Carbon/nitrogen homeostasis control in cyanobacteria

“…For details on the GS-GOGAT cycle and its mode of regulation, the readers are referred to comprehensive reviews on cyanobacterial ammonium assimilation (Herrero, Muro-Pastor and Flores 2001 ; Muro-Pastor, Reyes and Florencio 2005 ; Luque and Forchhammer 2008 ; Bolay et al . 2018 ). To avoid a detrimental depletion of the cellular glutamate pool by GS, its activity must be tightly adjusted to the capacity of the GOGAT reaction to refill the glutamate pool.…”

The Novel P II -Interacting Protein PirA Controls Flux into the Cyanobacterial Ornithine-Ammonia Cycle

“…Simultaneously, enhanced DNA binding of NtcA represses the transcription of the genes gifA and gifB , encoding the two known IFs, IF7 and IF17 ( 33 ). GS activity thereby is tuned in a trade-off between cellular N demands and relief from the metabolic burden imposed by the glutamate- and ATP-consuming GS-catalyzed reaction (for a review, see reference 88 ). Besides gifA and gifB , only a few other genes appear to be negatively regulated by NtcA.…”

Small but Smart: On the Diverse Role of Small Proteins in the Regulation of Cyanobacterial Metabolism

“…It tightly controls IF17 synthesis in response to a glutamine threshold that is passed when GS activity, i.e., glutamine synthesis exceeds a certain level [44]. The peculiarities of the complex regulation of GS by direct interaction with the small proteins IF7 and IF17 are also reviewed elsewhere in more detail [45]. However, it should be noted that although IFs are unique to cyanobacteria, GS regulation by small proteins is not restricted to this group per se.…”