There are various routes employed by bacteria to utilize arginine. While the first arginine catabolic operon was reported in 1990 on the arginine deiminase (ADI) pathway, the past decade has proven to be enormously productive regarding molecular characterization of various arginine catabolic operons and regulation in bacteria.

In this Subsystem we summarize four major arginine catabolic pathways:

1) arginase pathway,
2) arginine succinyltransferase (AST) pathway (the major route of arginine utilization as the carbon and nitrogen source under aerobic conditions),
3) arginine decarboxylase/agmatinase/agmatine deiminase pathway (serves to supply putrescine when arginine is abundant),
4) arginine deiminase (ADI) pathway ( there is separate Subsystem in the SEED for ADI: Arginine Deiminase Pathway, Author: master:OlgaZ) (provides ATP to support slow growth under anaerobic conditions).

=======Variant codes: ===============

1.1 - Arginine succinyltransferase (AST) pathway (astCADBE operon);
1.2 – Arginase pathway (rocRDEF or rocRDGA operons)
1.3 – Arginine decarboxylase/agmatinase/agmatine deiminase pathway (SpeA or AdiA +SpeB or AguAB);
1.4 - Arginine deiminase (ADI) pathway;

1.1234 - All routes above are present and complete;
1.12x34 - All routes above are present and complete except arginase pathway (code1.2), where some genes are missing.

“x” after the number stands for incomplete pathway

This subsystem was originally encoded by master:MattC (see Subsystem: Arginine_Putrescine_and_4-aminobutyrate_degradation in Clearing House)

====== =======Arginase pathway===================

While arginase is well known of its function in urea cycle of eukaryotes, it also serves as the first enzyme of the arginase pathway for arginine utilization in many microorganisms. In bacteria, this pathway was best studied in bacilli and Agrobacterium. In B. subtilis, enzymes and permeases of this pathway are encoded by rocABC and rocDEF operons, as well as rocG which is divergently transcribed from. After release of urea from L-arginine by arginase (RocF), the resulting ornithine is further catabolized into glutamate by ornithine aminotransferase (RocD) and delta-pyrroline-5-carboxylate dehydrogenase (RocA). The rocG gene encodes a catabolic glutamate dehydrogenase (GDH) that produces 2-ketoglutarate from glutamate. This provides the potential for some bacteria to utilize arginine as the sole source of carbon and nitrogen, wherein urea released by arginase can be used as the nitrogen source in the presence of urease. The roc operon structures as characterized in B. subtilis are not conserved among bacilli. The RocD, RocF, and RocA homologues are scattered on genomes of most bacilli, and only partial conversation in operon structure can be found in Bacillus licheniformis (rocRDEF) and Bacillus halodurans (rocRDGA).
A strong induction of the arginase pathway could also be beneficial for pathogenic bacteria in host invasion. In this regard, it is interesting to note that in Helicobacter pylori arginase plays a role in inhibition of nitric oxide synthesis in macrophages by depletion of l-arginine. As this is the rate-limiting substrate of nitric oxide synthetase in vivo, it serves as a strategy for bacterial survival.

=======Arginine succinyltransferase (AST) pathway==============

This pathway was first discovered in pseudomonads, identification and characterization of the aruCFGDBE operon encoding enzymes of the AST pathway in P. aeruginosa was reported by Itoh in 1997.
It serves as the primary route for arginine and ornithine utilization as the carbon source under aerobic conditions. The aru operon is located immediately downstream of the aotJQMOP-argR operon encoding components of an ABC transporter for arginine and ornithine as well as the arginine regulatory protein ArgR. The organization of these operons is highly conserved among pseudomonads and Burkholderia. Such an organization might provide an advantage in response to exogenous L-arginine in these bacteria, which can utilize L-arginine very efficiently as the sole source of carbon and nitrogen.
Identification of the aru operon in P. aeruginosa immediately led to the discovery of its functional homologue by sequence comparison in many other bacteria, including enteric bacteria (E. coli, Salmonella typhi, Salmonella typhimurium, and Yersinia pestis), Vibrio, Caulobacter, and Shewanella. No aru homologues have been found in identified Gram-positive bacteria. In E. coli and S. typhimurium, the astCADBE operon is essential for growth on arginine as a poor source of nitrogen.

========Arginine decarboxylase/agmatinase/agmatine deiminase pathway====

This pathway is essentially identical to an anabolic pathway that is used by many bacteria for the biosynthesis of putrescine. Even though the main catabolic arginine pathway of Escherichia coli K-12 is the succinyltransferase pathway, this pathway provides an alternative route, and is used under certain growth conditions.
Escherichia coli K-12 has two forms of the enzyme arginine decarboxylase: a constitutive biosynthetic form, encoded by the speA gene, and an inducible catabolic form, encoded by the adiA gene. When the catabolic form is not expressed, the pathway operates only in an anabolic manner, catalyzing the biosynthesis of putrescine , which is used by the bacteria either directly or as a precursor for the biosynthesis of other polyamines. When the cells are grown in an arginine-rich medium, the catabolic arginine decarboxylase is expressed, and the pathway operates in a catabolic manner, feeding putrescine via 4-aminobutyrate and succinate into the TCA cycle.

=====Arginine deiminase(ADI) pathway========

See description of this pathway in the Subsystem: Arginine Deiminase Pathway, Author: master:OlgaZ.

==========Arginine Transport systems:===================

Three uptake systems for the nitrogen and energy-rich basic amino acid arginine have been described so far in Escherichia coli K-12:
(i) the arginine-specific system;
(ii) the AO system for arginine and ornithine;
(iii) the LAO system for basic amino acids (lysine, arginine, ornithine.

The three transport systems for arginine differ on the substrate specificity, the affinity for L-arginine, and the regulation of their synthesis and activity. All these features suggest that they serve different physiological needs and are mobilized in distinct conditions.

The LAO system is encoded by the argT-hisJQMP locus composed of two transcriptional units of the same polarity. It is the best characterized of the three transport systems. It was first discovered in E. coli and has been best studied in Salmonella typhimurium. The gene cluster comprises two periplasmic binding proteins: the argT encoded LAO protein that binds lysine, arginine (KD 1.5 É M) and ornithine, and HisJ that binds histidine (KD 0.11 É M) and arginine (KD 10 É M). ArgT (LAO) and HisJ share 70% amino acid sequence identity. They combine with the same ABC-type transport complex, HisQMP2 that consists of the integral membrane proteins HisQ and HisM, and two membrane-associated HisP subunits that carry the ATP-binding motif and energize the transporter. S. typhimurium has several transport systems for histidine, but the HisJQMP2 complex might be the sole transport system for histidine in E. coli.

Both the arginine-specific and the AO (arginine and ornithine) uptake system of E. coli are encoded by the artPIQM-artJ locus (art for arginine transport) that is organized in two transcriptional units of identical polarity. A similar locus can be detected in the genome of S. typhimurium. The ArtQ, ArtM and ArtP proteins are similar to the components of the HisQMP2 membrane-bound complex. ArtJ is the previously characterized arginine-specific periplasmic binding protein ArgBP-I. Isolated ArtJ binds L-arginine (Kd 0.4 É M), but not ornithine.

The E. coli artJ, artPIQM and hisJQMP genes and operons were recently discovered as new members of the ArgR regulon. The hexameric repressor protein ArgR is the master regulator of this regulon. In the presence of arginine, ArgR inhibits the transcription of several biosynthetic and transport genes/operons, and its own synthesis. Liganded ArgR also functions as a co-activator of the astCADBE operon encoding the arginine succinyltransferase pathway for arginine catabolism.

---------- Regulation (ArgR/AhrC):----------------

Despite differences in the organization of genes in arginine metabolism, the ArgR proteins and their cognate target sites are highly conserved among very diverse organisms, including Gram-positive (AhrC of B. subtilis), Gram-negative, and extremophiles. In general, regulation is exerted by binding of ArgR to its operator sites preceding the target genes, leading to repression of arginine biosynthetic genes and activation of catabolic genes in the presence of arginine. Although exhibiting low sequence similarity, crystal structures of ArgR from E. coli, Bacillus stearothermpohilus, and B. subtilis revealed a highly conserved structure organization and fold.
From bacterial genome sequence analysis, it is known that several low-G + C Gram-positive organisms possess multiple ArgR homologues. In E. faecalis, the divergently transcribed argR1 and argR2 are differentially expressed in response to arginine and glucose, and these two genes were proposed to control arginine-dependent induction of the downstream arc operon for the ADI pathway. In Lactococcus lactis, argR and ahrC have been identified as essential genes for arginine-dependent regulation of genes in arginine biosynthesis and catabolism.

=======REFERENCES=====================

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