Regulatory Links Between Carbon And Nitrogen Metabolism

Regulatory links between carbon and nitrogen metabolism
¨ ¨ Fabian M Commichau1, Karl Forchhammer2 and Jorg Stulke1
The metabolism of carbon- and nitrogen-containing compounds is fundamental to all forms of life. To cope with changing environmental conditions, bacteria have to sense the nutrient supply and adapt their metabolism accordingly. In addition to nutrient- and pathway-specificresponses, they integrate information from the different branches of metabolism to coordinate the control of the expression of many metabolic genes. Two major players interconnecting carbon and nitrogen regulation are the PII proteins and the phosphotransferase system. Moreover, several DNA-binding transcription regulators sense signals are derived from both carbon and nitrogen metabolism. The regulatorynetworks enable the bacteria to make the appropriate metabolic responses to changing nutrient availabilities in the environment.
Addresses 1 Department of General Microbiology, Institute of Microbiology and ¨ Genetics, Georg-August University Gottingen, Grisebachstr. 8, ¨ D-37077 Gottingen, Germany 2 ¨ Institut fur Mikrobiologie und Molekularbiologie, Justus-Liebig¨ Universitat Giessen,Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany ¨ ¨ Corresponding author: Stulke, Jorg (jstuelk@gwdg.de)

Coordinated regulation of gene expression has long been studied for genes involved in the metabolism of compounds that are directly related to different branches of metabolism. For example, the utilization of amino acids that serve as a source of both carbon and nitrogen is under dual control bythe carbon and nitrogen signalling systems [1,2]. By contrast, the regulatory interdependence of different metabolic routes has only recently attracted interest. It is now clear that carbon metabolism is not only controlled by carbon-derived signals, but also by the availability of nitrogen and other nutrients. Similarly, the metabolism of nitrogen, sulphur, phosphorus and iron in bacteria iscontrolled by the carbon source, in addition to their cognate metabolic signals [3–6]. In this review we give an overview on the recent work in the field of the regulatory interactions between carbon and nitrogen metabolism in bacteria. Two of the major signal transduction systems of carbon and nitrogen metabolism are involved: PII, a small nitrogen regulatory protein, and the phosphotransferase system(PTS). Because of their important role in regulatory functions, PII and the PTS can be regarded as the ‘central processing units’ of nitrogen and carbon metabolism, respectively. In addition to these systems, several transcriptional regulators have been identified that coordinate carbon and nitrogen metabolism.

Current Opinion in Microbiology 2006, 9:167–172 This review comes from a themed issueon Cell regulation Edited by Werner Geobel and Stephen Lory Available online 2nd February 2006 1369-5274/$ – see front matter # 2005 Elsevier Ltd. All rights reserved. DOI 10.1016/j.mib.2006.01.001

PII senses the energy, carbon and nitrogen status of the cell
The members of the PII protein family are present in bacteria, methanogenic archaea and phototrophic eukaryotes, where they are centralto the control of nitrogenassimilatory processes. They sense 2-oxoglutarate and ATP and thus, link the state of a central carbon and energy metabolite to the control of nitrogen assimilation [7,8,9]. In addition, they can be covalently modified and thereby integrate additional signals, such as glutamine (see below). Because the various binding and modification events mutually influence each other,signal input by PII results in a complex array of covalent and non-covalent modification states. Depending on these, the PII proteins bind to various receptors (central regulators and/or metabolic enzymes of nitrogen assimilation) and modulate their activities (Figure 1). Organisms of different phylogenetic lineages have evolved a wide diversity of PII–receptor interactions, adjusted to their...