L-arginine biosynthesis in Pseudomonas fluorescens FW300-N2C3

GapMind for Amino acid biosynthesis

L-arginine biosynthesis in Pseudomonas fluorescens FW300-N2C3

Best path

argA, argB, argC, argD, argE, carA, carB, argI, argG, argH

Also see fitness data for the top candidates

Rules

Overview: Arginine biosynthesis in GapMind is based on MetaCyc pathways L-arginine biosynthesis I via L-acetyl-ornithine (link), II (acetyl cycle) (link), III via N-acetyl-L-citrulline (link), or IV via LysW-ornithine (link). GapMind also includes L-arginine biosynthesis with succinylated intermediates, as in Bacteroidetes (PMC5764234). These pathways all involve the activation of glutamate (by aceylation, succinylation, or attachment of LysW), followed by phosphorylation, reduction and transamination, to activated ornithine. In most pathways, this intermediate is cleaved to ornithine before transcarbamoylation, but in the N-acetylcitrulline or succinylated pathways, transcarbamoylation occurs before hydrolysis. In the final two steps, citrulline is converted to arginine by ArgG and ArgH.

all:

ornithine, carA, carB, argI, argG and argH
or argA, argB, argC, argD, carA, carB, argF', argE, argG and argH
or argA, argB, argC, argD'B, argF'B, argE'B, argG and argH
Comment: In pathways I, II, or IV, ornithine is carbamoylated by argI. In pathway III (N-acetylcitrulline), N-acetylornithine is carbamoylated by argF' and N-acetylcitrulline is hydrolyzed by argE. In the pathway with succinylated intermediates, N-succinylornithine is carbamoylated by argF'B.

ornithine:

argA, argB, argC, argD and argE
or argJ, argB, argC and argD
or lysW, argX, lysZ, lysY, lysJ and lysK
Comment: In L-arginine biosynthesis I, ornithine forms via acetylated intermediates, argA, and argE (link). In L-arginine biosynthesis II, ornithine forms via acetylated intermediates and argJ (link). In L-arginine biosynthesis IV, ornithine forms via LysW-modified intermediates (link).

21 steps (17 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argA	N-acylglutamate synthase	AO356_13085	AO356_17930
argB	N-acylglutamate kinase	AO356_12525	AO356_13085
argC	N-acylglutamylphosphate reductase	AO356_14490	AO356_24070
argD	N-acetylornithine aminotransferase	AO356_18725	AO356_10715
argE	N-acetylornithine deacetylase	AO356_25400	AO356_13080
carA	carbamoyl phosphate synthase subunit alpha	AO356_07485	AO356_14430
carB	carbamoyl phosphate synthase subunit beta	AO356_07480
argI	ornithine carbamoyltransferase	AO356_05275	AO356_18275
argG	arginosuccinate synthetase	AO356_18325
argH	argininosuccinate lyase	AO356_12780	AO356_29670
Alternative steps:
argD'B	N-succinylornithine aminotransferase	AO356_18725	AO356_17010
argE'B	N-succinylcitrulline desuccinylase
argF'	acetylornithine transcarbamoylase	AO356_18275
argF'B	N-succinylornithine carbamoyltransferase
argJ	ornithine acetyltransferase	AO356_12410	AO356_17930
argX	glutamate--LysW ligase	AO356_10160
lysJ	[LysW]-glutamate-semialdehyde aminotransferase	AO356_18725	AO356_17010
lysK	[LysW]-ornithine hydrolase
lysW	2-aminoadipate/glutamate carrier protein
lysY	[LysW]-glutamate-6-phosphate reductase	AO356_14490
lysZ	[LysW]-glutamate kinase	AO356_12525

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Apr 09 2024. The underlying query database was built on Apr 09 2024.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

the paper from 2019 on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer
changes to Amino acid biosynthesis since the publication.

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for Amino acid biosynthesis