Definition of D-glucuronate catabolism

GapMind for catabolism of small carbon sources

Definition of D-glucuronate catabolism

# Glucuronate utilization in GapMind is based on MetaCyc pathways
# D-glucuronate degradation II (oxidation of 5-keto-4-deoxyglucarate, metacyc:PWY-6501),
# a related pathway via 5-keto-4-deoxyglucarate aldolase (metacyc:PWY-6516),
# or degradation via fructuronate (metacyc:PWY-7247).
# GapMind also includes a variation on the oxidative pathway with a glucarolactonase, as in Pseudomonas putida.
# MetaCyc pathway I (via L-gulonate and xylitol, metacyc:PWY-5525) is not reported in prokaryotes
# and is not described here.

exuT	D-glucuronate:H+ symporter ExuT	curated:SwissProt::P0AA78	curated:TCDB::P0AA78	curated:TCDB::P94774

# Transporters were identified using
# query: transporter:glucuronate:D-glucuronate:D-glucopyranuronate:CPD-14488:CPD-12521:CPD-15530
glucuronate-transport: exuT

# Genetic data from Pseudomonas putida suggests the involvement of a TRAP transporter:
# dctP-like PP_1169 (Q88NN8),
# dctQ-like PP_1168 (Q88NN9),
# and dctM-like PP_1167 (Q88NP0).
# Furthermore, PP_1169 is nearly identical to Pput_1203, which binds D-glucuronate
# (see PMC4310620 and PDB:4xfeA).
# The related substrate-binding proteins Bpro_3107 (Q128M1) and Bamb_6123 (Q0B2F6)
# was also shown to bind D-glucuronate (and D-galacturonate).
dctP	D-glucuronate TRAP transporter, solute receptor component	uniprot:Q88NN8	curated:SwissProt::Q128M1	curated:SwissProt::Q0B2F6
dctQ	D-glucuronate TRAP transporter, small permease component	uniprot:Q88NN9
dctM	D-glucuronate TRAP transporter, large permease component	uniprot:Q88NP0
glucuronate-transport: dctP dctQ dctM

# Porin OdpF was ignored

# 5-dehydro-4-deoxyglucarate is an intermediate in glucuronate catabolism.

import galacturonate.steps:kdgD # 5-dehydro-4-deoxyglucarate dehydratase
import xylose.steps:dopDH # 2,5-dioxopentanonate dehydrogenase

# As part of pathway II, 5-dehydro-4-deoxyglucarate is dehydrated/decarboxylated to
# 2,5-dioxopentanoate (by kdgD) and oxidized to 2-oxoglutarate (by dopDH).
5-dehydro-4-deoxyglucarate-degradation: kdgD dopDH

garL	5-dehydro-4-deoxy-D-glucarate aldolase	EC:4.1.2.20

# glxR (G6278-MONOMER) is linked to this reaction (but not this EC) in ecocyc and metacyc.
# PGA1_c14880 (Phaeo:GFF1469) had been reannotated as a tartronate semialdehyde reductase but
# this is questionable.
garR	tartronate semialdehyde reductase	EC:1.1.1.60	curated:ecocyc::G6278-MONOMER	ignore:reanno::Phaeo:GFF1469

import deoxyribonate.steps:garK # glycerate 2-kinase

# Alternatively, 5-dehydro-4-deoxy-D-glucarate can be consumed by aldolase garL,
# which forms pyruvate and tartronate semialdehyde (2-hydroxy-3-oxopropionate);
# tartronate semialdehyde is reduced to D-glycerate and phosphorylated
# to enter glycolysis.
5-dehydro-4-deoxyglucarate-degradation: garL garR garK

udh	D-glucuronate dehydrogenase	EC:1.1.1.203
gci	D-glucaro-1,4-lactone cycloisomerase	EC:5.5.1.27

# In pathway II, dehydrogenase udh forms D-glucaro-1,5-lactone, which spontaneously rearranges to
# D-glucaro-1,4-lactone, and the cycloisomerase gci forms 5-dehydro-4-deoxy-D-glucarate.
all: glucuronate-transport udh gci 5-dehydro-4-deoxyglucarate-degradation

# Biochemical studies showed that lactonases uxuL and uxuF act on
# D-glucaro-1,5-lactone (PMC6304669). These include
# Rpic_4446 = B2UIY8,
# PSPTO_1052 = Q888H2,
# Bcep1808_2255 = A4JG52,
# BMULJ_02167 = A0A0H3KPX2,
# Bcep18194_A5499 = Q39EM3,
# and PSPTO_2765 = Q881W7,
# Genetic data from P. putida KT2440
# shows that a uxuL-like protein (PP_1170 = Q88NN7) is involved in glucuronate
# utilization. UxuL/uxuF are also active on galactaro-1,5-lactone,
# and PS417_17365 from WCS417 may well act on both substrates, but this is not proven.
uxuL	D-glucaro-1,5-lactonase UxuL or UxuF	uniprot:B2UIY8	uniprot:Q888H2	uniprot:A4JG52	uniprot:A0A0H3KPX2	uniprot:Q39EM3	uniprot:Q881W7	uniprot:Q88NN7	ignore:reanno::WCS417:GFF3393

gudD	D-glucarate dehydratase	EC:4.2.1.40

# In P. putida, genetic data suggests that the lactone is hydrolyzed
# to D-glucarate by uxuL and the dehydratase gudD forms 5-dehydro-4-deoxy-D-glucarate.
all: glucuronate-transport udh uxuL gudD 5-dehydro-4-deoxyglucarate-degradation

uxaC	D-glucuronate isomerase	EC:5.3.1.12
# uxuB is D-mannonate oxidoreductase
# uxuA is D-mannonate dehydratase
import myoinositol.steps:uxuB uxuA
import glucosamine.steps:kdgK # 2-keto-3-deoxygluconate kinase
import glucose.steps:eda # 2-keto-3-deoxygluconate 6-phosphate aldolase

# In the fructuronate pathway, an isomerase (uxaC) converts D-glucuronate to D-fructuronate,
# followed by oxidation to D-mannonate, dehydration to
# 2-dehydro-3-deoxy-D-gluconate, phosphorylation to
# 2-dehydro-3-deoxy-D-gluconate 6-phosphate, and an aldolase reaction
# to glyceraldehyde-3-phosphate and pyruvate.
all: glucuronate-transport uxaC uxuB uxuA kdgK eda

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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:

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, 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

GapMind for catabolism of small carbon sources