GapMind for catabolism of small carbon sources

 

Definition of L-arginine catabolism

As text, or see rules and steps

# Arginine utilization in GapMind is based on MetaCyc pathways
# L-arginine degradation I via arginase (metacyc:ARGASEDEG-PWY);
# II via arginine succinyltransferase (metacyc:AST-PWY),
# III via arginine decarboxylase and agmatinase (metacyc:PWY0-823),
# IV via arginine decarboxylase and agmatine deiminase (metacyc:ARGDEG-III-PWY),
# V via arginine deiminase (metacyc:ARGDEGRAD-PWY),
# VI (arginase 2, metacyc:ARG-PRO-PWY),
# VII (arginase 3, metacyc:ARG-GLU-PWY),
# VIII via arginase oxidase (metacyc:ARGDEG-IV-PWY),
# IX via arginine:pyruvate transaminase (metacyc:PWY-5742),
# X via arginine monooxygenase (metacyc:ARGDEG-V-PWY),
# XIII via proline (metacyc:PWY-8187),
# and XIV via D-ornithine (metacyc:PWY-6344).
# Common intermediates are L-ornithine or L-proline.
# GapMind does not include pathways XI (metacyc:PWY-5024), which is poorly understood,
# or XII (metacyc:PWY-7523), which is not reported in prokaryotes.

# Many ABC transporters are known for arginine, including
# E. coli artJQMP (which is specific for arginine) and E. coli hisQPM-argT (also transports lysine, ornithine)
# These systems are generally homologous, but the two permease components also similar to each other.
# To simplify the analysis, these were clustered at 40% identity instead of the usual 30% identity.
# Distantly related proteins from Chlamydia (uniprot:ARTJ_CHLTR, uniprot:ARTJ_CHLPN) are annotated as artJ but
# are not actually characterized, and the other components of this
# system seem to be absent. So Chlamydial "artJ" were not included.
# Ignore hisJ (CH_018185) from Salmonella and the P. fluorescens lysine transporter (AO356_09900), which
# has a subtle defect on arginine and may well transport it, and close homologs in other Pseudomonas.
# In Marinobacter adhaerens, the SBP (HP15_3031, E4PNW5) is somewhat diverged, but fitness data
# confirms it is involved.
artJ	L-arginine ABC transporter, periplasmic substrate-binding component ArtJ/HisJ/ArtI/AotJ/ArgT	curated:reanno::pseudo3_N2E3:AO353_03055	curated:CharProtDB::CH_002541	curated:CharProtDB::CH_003045	curated:CharProtDB::CH_014295	curated:SwissProt::P30859	curated:TCDB::O50181	curated:TCDB::P09551	curated:TCDB::Q9HU31	curated:reanno::BFirm:BPHYT_RS07735	curated:reanno::WCS417:GFF4245	curated:reanno::pseudo1_N1B4:Pf1N1B4_3431	curated:reanno::pseudo5_N2C3_1:AO356_18700	curated:reanno::pseudo6_N2E2:Pf6N2E2_5660	ignore:CharProtDB::CH_018185	ignore:reanno::pseudo5_N2C3_1:AO356_09900	ignore:reanno::pseudo6_N2E2:Pf6N2E2_2958	ignore:reanno::pseudo5_N2C3_1:AO356_05495	uniprot:E4PNW5

# ArtM and HisM are distantly related and were combined.
# TC 1.B.6.2.7 / F9GZA7 is annotated as ArtM but seems more likely to be an outer membrane porin,
# so it is not included.
# Ignore closely related lysine transporters from P. fluorescens (which may well transport arginine;
# AO356_09910 has a subtle defect in arginine utilization).
artM	L-arginine ABC transporter, permease component 1 (ArtM/HisM/AotM)	curated:SwissProt::P0A2I7	curated:SwissProt::P0AEU3	curated:TCDB::O50183	curated:TCDB::Q9HU29	curated:reanno::BFirm:BPHYT_RS07680	curated:reanno::WCS417:GFF4243	curated:reanno::pseudo1_N1B4:Pf1N1B4_3433	curated:reanno::pseudo3_N2E3:AO353_03045	curated:reanno::pseudo5_N2C3_1:AO356_18710	curated:reanno::pseudo6_N2E2:Pf6N2E2_5662	curated:SwissProt::P0AE30	ignore:reanno::pseudo5_N2C3_1:AO356_09910	ignore:reanno::pseudo6_N2E2:Pf6N2E2_2960	ignore:reanno::pseudo5_N2C3_1:AO356_05505

# Ignore closely related lysine transporters from P. fluorescens (which may well transport arginine;
# AO356_09895 has a subtle defect in arginine utilization)
artP	L-arginine ABC transporter, ATPase component ArtP/HisP/AotP/BgtA	curated:CharProtDB::CH_003210	curated:SwissProt::P02915	curated:SwissProt::P0AAF6	curated:SwissProt::P54537	curated:TCDB::O30506	curated:TCDB::P73721	curated:TCDB::Q9HU32	curated:reanno::BFirm:BPHYT_RS07685	curated:reanno::pseudo1_N1B4:Pf1N1B4_3435	curated:reanno::pseudo3_N2E3:AO353_03040	curated:reanno::pseudo5_N2C3_1:AO356_18715	curated:reanno::pseudo6_N2E2:Pf6N2E2_5663	ignore:reanno::pseudo5_N2C3_1:AO356_09895	ignore:reanno::pseudo5_N2C3_1:AO356_05515	ignore:reanno::pseudo6_N2E2:Pf6N2E2_2962

# Ignore closely related lysine transporters in P. fluorescens (which may well transport arginine;
# AO356_09905 has a subtle defect in arginine utilization)
artQ	L-arginine ABC transporter, permease component 2 (ArtQ/HisQ/AotQ)	curated:TCDB::Q9HU30	curated:CharProtDB::CH_107317	curated:SwissProt::P0A2I9	curated:SwissProt::P0AE34	curated:SwissProt::P52094	curated:reanno::BFirm:BPHYT_RS07675	curated:reanno::WCS417:GFF4244	curated:reanno::pseudo1_N1B4:Pf1N1B4_3432	curated:reanno::pseudo3_N2E3:AO353_03050	curated:reanno::pseudo5_N2C3_1:AO356_18705	curated:reanno::pseudo6_N2E2:Pf6N2E2_5661	ignore:reanno::pseudo5_N2C3_1:AO356_09905	ignore:reanno::pseudo6_N2E2:Pf6N2E2_2959	ignore:reanno::pseudo5_N2C3_1:AO356_05500

# Transporters were identified using:
# query: transporter:arginine:L-arginine:arg.
arginine-transport: artJ artM artP artQ 

# In a artJMPQ-like system from Synechocystis, there is just one permease component fused to the
# substrate-binding component. The fusion protein is known as BgtB or BgtAB.
# (BgtA is the ATPase component and is included in the definition of ArtP.)
bgtB	L-arginine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)	curated:TCDB::P73544	curated:TCDB::Q8YSA2

arginine-transport: bgtB artP

# braCDEFG from Rhizobium leguminosarum is described in glutamate.steps
import glutamate.steps:braC braD braE braF braG
arginine-transport: braC braD braE braF braG

# Homomeric transporters

rocE	L-arginine permease	curated:CharProtDB::CH_091412	curated:CharProtDB::CH_091699	curated:SwissProt::A0A1D8PPG4	curated:SwissProt::A0A1D8PPI5	curated:SwissProt::P39137	curated:SwissProt::Q59WB3	curated:SwissProt::Q59WU0	curated:SwissProt::Q5AG77	curated:TCDB::P43059
arginine-transport: rocE

AAP3	L-arginine transporter AAP3	curated:BRENDA::Q86G79
arginine-transport: AAP3

CAT1	L-arginine transporter CAT1	curated:CharProtDB::CH_091324
arginine-transport: CAT1

Can1	L-arginine transporter Can1	curated:CharProtDB::CH_124821
arginine-transport: Can1

# Arginine/ornithine antiporters were ignored, as if ornithine is secreted during
# growth on arginine then CO2 would be the effective carbon source.
# Similarly, arginine/agmatine antiporters were ignored.

# Arginine and lysine exporters (argO/yggA/lysE) were ignored
# Eukaryotic ornithine carrier proteins were ignored, as these export ornithine/arginine
# Vacuolar and lysosomal amino acid transporters were ignored
# Outer membrane porins (oprD2 and "artM", TC 1.B.6.2.7) were ignored
# A family of metazoan amino acid transporters (TC 2.A.3.8) was ignored

# putrescine and GABA (gamma-aminobutyrate) are common intermediates.
# MetaCyc does not list putrescine catabolism with glutamylated intermediates
# (puuABCD) as a pathway for arginine (or citrulline) utilization, but it is logical that
# arginine and citrulline can be converted to putrescine and catabolized this way.
# Fitness data suggests that puuA is involved in arginine utilization
# in Pseudomonas fluorescens FW300-N2E3 and in Pseudomonas simiae WCS417.
import putrescine.steps:putrescine-degradation GABA-degradation

# Proline is an intermediate
import leucine.steps:atoB # acetyl-CoA acetyltransferase is part of glutaryl-CoA degradation
import phenylacetate.steps:glutaryl-CoA-degradation # glutaryl-CoA is part of 5-aminovalerate degradation
import lysine.steps:5-aminovalerate-degradation # 5-aminovalerate-degradation is part of proline degradation
import proline.steps:proline-degradation

# Pseudomonas aeruginsa has a heteromeric succinyltransferase (AruFG) that
# is active on both arginine and ornithine (PMID:7523119, PMID:9393691).
aruF	ornithine/arginine N-succinyltransferase subunit AruAI (AruF)	curated:CharProtDB::CH_107315
aruG	ornithine/arginine N-succinyltransferase subunit AruAII (AruG)	curated:BRENDA::P80358
arginine-succinyltransferase: aruF aruG

# The other known arginine N-succinyltransferases have just one subunit
# and are not known to be active on ornithine.
astA	arginine N-succinyltransferase	EC:2.3.1.109	ignore:CharProtDB::CH_107315	ignore:BRENDA::P80358
arginine-succinyltransferase: astA

# Marinobacter adhaerens HP15_3042 (GFF3099) is important for arginine biosynthesis
# as well as catabolism, suggesting it is succinylornithine transaminase and
# acetylornithine transaminase (similar to P. aeruginosa aruC)
astC	succinylornithine transaminase	EC:2.6.1.81	curated:reanno::Marino:GFF3099

astD	succinylglutamate semialdehyde dehydrogenase	EC:1.2.1.71
astE	succinylglutamate desuccinylase	EC:3.5.1.96

# Ornithine is a common intermediate. It can be succinylated by aruFG and then
# catabolized by the later steps of the arginine succinyltransferase pathway, via
# aminotransferase, dehydrogenase, and desuccinylase reactions (see
# PMC179677 and PMID:7523119).
ornithine-degradation: aruF aruG astC astD astE

rocD	ornithine aminotransferase	EC:2.6.1.13
rocA	1-pyrroline-5-carboxylate dehydrogenase	EC:1.2.1.88

# Or as part of L-arginine degradation I, the
# aminotransferase rocD converts ornithine to glutamate 5-semialdehyde,
# which spontaneously converts to 1-pyrroline-5-carboxylate.  A
# dehydrogenase converts this to glutamate.
ornithine-degradation: rocD rocA

PRO3	pyrroline-5-carboxylate reductase	EC:1.5.1.2
# Or 1-pyrroline-5-carboxylate can be reduced to proline by PRO3, as in L-arginine degradation VI.
ornithine-degradation: rocD PRO3 proline-degradation

ocd	ornithine cyclodeaminase	EC:4.3.1.12

# Alternatively, ornithine can be converted directly to proline
# by ornithine cyclodeaminase (ocd).
ornithine-degradation: ocd proline-degradation

odc	L-ornithine decarboxylase	EC:4.1.1.17

# Or ornithine can be decarboxylated to putrescine by odc (metacyc:ORNDEG-PWY).
ornithine-degradation: odc putrescine-degradation

orr	ornithine racemase	EC:5.1.1.12
# D-ornithine aminomutase (5.4.3.5) is heteromeric
oraS	D-ornithine 4,5-aminomutase, alpha (S) subunit	curated:SwissProt::E3PY96	ignore_other:5.4.3.5
oraE	D-ornithine 4,5-aminomutase, beta (E) subunit	curated:SwissProt::E3PY95	ignore_other:5.4.3.5
ord	2,4-diaminopentanoate dehydrogenase	EC:1.4.1.12
# 2-amino-4-oxopentanoate thiolase (2.3.1.263) is heteromeric
ortA	2-amino-4-oxopentanoate thiolase, alpha subunit	curated:SwissProt::C1FW06	curated:SwissProt::E3PY98	ignore_other:2.3.1.263
ortB	2-amino-4-oxopentanoate thiolase, beta subunit	curated:SwissProt::C1FW07	curated:SwissProt::E3PY97	ignore_other:2.3.1.263

# Or ornithine can be catabolized via D-ornithine, as in L-arginine
# degradation XIV. A racemase converts L-ornithine to D-ornithine; an
# aminomutase forms (2R,4S) 2,4-diaminopentanoate; a dehydrogenase
# forms (2R)-2-amino-4-oxopentanoate, and a thiolase cleaves it to
# D-alanine and acetyl-CoA. D-alanine could be oxidized to pyruvate or
# perhaps secreted; this is not described here.
ornithine-degradation: orr oraS oraE ord ortA ortB

rocF	arginase	EC:3.5.3.1

# Pathways I, VI, or VII begin with rocF (arginase), which forms ornithine and urea. (The urea might not be utilized, so urease is not described here.) They differ in how the ornithine is catabolized.
all: arginine-transport rocF ornithine-degradation


astB	N-succinylarginine dihydrolase	EC:3.5.3.23

# Pathway II begins with arginine succinyltransferase and ends with succinate and glutamate.
# The succinate would then be activated to
# succinyl-CoA to restart the cycle, or the glutamate
# might be oxidized to succinyl-CoA; these
# steps are not included here.
all: arginine-transport arginine-succinyltransferase astB astC astD astE

# Q5R145 is misannotated in BRENDA.
adiA	arginine decarboxylase (AdiA/SpeA)	EC:4.1.1.19	ignore:BRENDA::Q5R145
speB	agmatinase	EC:3.5.3.11

# Pathway III begins with decarboxylation to agmatine by adiA, followed by hydrolysis to putrescine and urea.
all: arginine-transport adiA speB putrescine-degradation

# Q89413 is misannotated in BRENDA
aguA	agmatine deiminase	EC:3.5.3.12	ignore:BRENDA::Q89413
aguB	N-carbamoylputrescine hydrolase	EC:3.5.1.53	ignore:BRENDA::Q89413

# Pathway IV begins with adiA and agmatine deiminase (aguA), which yields
# N-carbamoylputrescine; this is hydrolyzed to putrescine and urea.
all: arginine-transport adiA aguA aguB putrescine-degradation

# Some diverged members of this family had been reannotated as arginine deiminases,
# putatively involved in citrulline catabolism by the reverse reaction.
# However, the reverse reaction is thermodynamically quite unfavorable; more likely,
# these proteins have a different function
arcA	arginine deiminase	EC:3.5.3.6	ignore:reanno::Phaeo:GFF1616	ignore:reanno::WCS417:GFF3434	ignore:reanno::pseudo3_N2E3:AO353_25635

# arcB forms carbamoyl-phosphate and ornithine
arcB	ornithine carbamoyltransferase	EC:2.1.3.3

# arcC from P. aeruginosa (P13982) was studied both biochemically and genetically
# and linked to sequence by PMID:2537202
arcC	carbamate kinase	EC:2.7.2.2	uniprot:P13982

# Pathway V begins with arginine deiminase (arcA), forming citrulline, and 
# and a carbamoyltransferase
# forms carbamoyl-phosphate and ornithine.
# The carbamoyl-phosphate is consumed by carbamate kinase (in reverse,
# forming ammonia and CO2 and ATP).
all: arginine-transport arcA arcB arcC ornithine-degradation

aroD	L-arginine oxidase	EC:1.4.3.25
aruI	2-ketoarginine decarboxylase	EC:4.1.1.75
kauB	4-guanidinobutyraldehyde dehydrogenase	EC:1.2.1.54
gbuA	guanidinobutyrase	EC:3.5.3.7

# Pathway VIII begins with arginine oxidase aroD, which forms 5-guanidino-2-oxopentanoate (2-ketoarginine);
# this is converted to gamma-aminobutyrate (GABA).
all: arginine-transport aroD aruI kauB gbuA GABA-degradation

aruH	L-arginine:pyruvate transaminase	EC:2.6.1.84

# Pathway IX is similar to pathway VIII but the transaminase aruH forms the 5-guanidino-2-oxopentanoate.
all: arginine-transport aruH aruI kauB gbuA GABA-degradation

# arginine monooxygenase (EC 1.13.12.1) was linked to sequence by PMID:24218293,
# but does not appear in any of the curated databases.
# They showed that STRVN_2699 and STRVN_6565 are arginine monooxygenases;
# these correspond to SMALA_2699 (A0A291SPZ4) and SMALA_6565 (A0A291T0Y3)
arg-monooxygenase	arginine 2-monooxygenase	uniprot:A0A291SPZ4	uniprot:A0A291T0Y3

# This enzyme is not linked to sequence in MetaCyc (which gives it the
# EC 3.5.1.4, for broad-specificity amidases). PMID:24218293 showed
# that STRVN_6564 (SMALA_6564,A0A291T0X0) and _7510 (A0A291T3M3)
# perform this reaction.  And PMID:24752846 showed that A0A088BHP3
# (azl13, see genbank KF772886.1) performs this reaction. (It is
# annotated in BRENDA as an amidase.)
gbamidase	guanidinobutyramidase	uniprot:A0A291T0X0	uniprot:A0A291T3M3	curated:BRENDA::A0A088BHP3

# Pathway X involves
# arginine 2-monooxygenase (decarboxylating), forming 4-guanidinobutyramide,
# and an amidase, forming 4-guanidinobutyrate, which is consumed as
# in pathway VIII or IX.
all: arginine-transport arg-monooxygenase gbamidase kauB gbuA GABA-degradation

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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:

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:

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:

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, or view the source code.

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