Definition of D-glucuronate catabolism
As rules and steps, or see full text
Rules
Overview: Glucuronate utilization in GapMind is based on MetaCyc pathways D-glucuronate degradation II (oxidation of 5-keto-4-deoxyglucarate, link), a related pathway via 5-keto-4-deoxyglucarate aldolase (link), or degradation via fructuronate (link). GapMind also includes a variation on the oxidative pathway with a glucarolactonase, as in Pseudomonas putida. MetaCyc pathway I (via L-gulonate and xylitol, link) is not reported in prokaryotes and is not described here.
- all:
- glucuronate-transport, udh, gci and 5-dehydro-4-deoxyglucarate-degradation
- or glucuronate-transport, udh, uxuL, gudD and 5-dehydro-4-deoxyglucarate-degradation
- or glucuronate-transport, uxaC, uxuB, uxuA, kdgK and eda
- Comment: 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. 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. 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.
- 5-dehydro-4-deoxyglucarate-degradation:
- kdgD and dopDH
- or garL, garR and garK
- Comment: 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). 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.
- glucuronate-transport:
- exuT
- or dctP, dctQ and dctM
- Comment: Transporters were identified using query: transporter:glucuronate:D-glucuronate:D-glucopyranuronate:CPD-14488:CPD-12521:CPD-15530
Steps
exuT: D-glucuronate:H+ symporter ExuT
- Curated sequence P0AA78: Hexuronate transporter. hexuronate transporter. hexuronate transporter
- Curated sequence P0AA78: Hexuronate (glucuronate; galacturonate) porter, ExuT (Nemoz et al. 1976). It also transports D-glucose (HJ Kim et al., Front. Microbiol., 23 January 2020)
- Curated sequence P94774: The Aldohexuronate (glucuronate, galacturonate) uptake porter
- Total: 3 characterized proteins
dctP: D-glucuronate TRAP transporter, solute receptor component
- UniProt sequence Q88NN8: SubName: Full=TRAP dicarboxylate transporter, DctP subunit {ECO:0000313|EMBL:AAN66793.1};
- Curated sequence Q128M1: Solute-binding protein Bpro_3107
- Curated sequence Q0B2F6: Solute-binding protein Bamb_6123
- Comment: 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).
- Total: 3 characterized proteins
dctQ: D-glucuronate TRAP transporter, small permease component
- UniProt sequence Q88NN9: SubName: Full=Putative TRAP dicarboxylate transporter, DctQ subunit {ECO:0000313|EMBL:AAN66792.1};
- Total: 1 characterized proteins
dctM: D-glucuronate TRAP transporter, large permease component
- UniProt sequence Q88NP0: SubName: Full=Putative TRAP dicarboxylate transporter, DctM subunit {ECO:0000313|EMBL:AAN66791.1};
- Total: 1 characterized proteins
kdgD: 5-dehydro-4-deoxyglucarate dehydratase
dopDH: 2,5-dioxopentanonate dehydrogenase
garL: 5-dehydro-4-deoxy-D-glucarate aldolase
garR: tartronate semialdehyde reductase
- Curated proteins or TIGRFams with EC 1.1.1.60
- Curated sequence G6278-MONOMER: tartronate semialdehyde reductase 2. tartronate semialdehyde reductase 2
- Ignore hits to GFF1469 when looking for 'other' hits (2-hydroxy-3-oxopropionate reductase (EC 1.1.1.60))
- Comment: 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.
- Total: 1 HMMs and 3 characterized proteins
garK: glycerate 2-kinase
- Curated proteins or TIGRFams with EC 2.7.1.165
- Curated sequence GFF1145: D-glycerate 2-kinase (EC 2.7.1.-)
- Comment: GarK produces 2-phospho-D-glycerate, an intermediate in glycolysis. psRCH2:GFF1145 is believed to do this reaction but was not annotated with this EC number.
- Total: 11 characterized proteins
udh: D-glucuronate dehydrogenase
gci: D-glucaro-1,4-lactone cycloisomerase
uxuL: D-glucaro-1,5-lactonase UxuL or UxuF
- UniProt sequence B2UIY8: SubName: Full=SMP-30/Gluconolaconase/LRE domain protein {ECO:0000313|EMBL:ACD29539.1};
- UniProt sequence Q888H2: SubName: Full=Senescence marker protein-30 family protein {ECO:0000313|EMBL:AAO54583.1};
- UniProt sequence A4JG52: SubName: Full=3-carboxymuconate cyclase-like protein {ECO:0000313|EMBL:ABO55255.1};
- UniProt sequence A0A0H3KPX2: SubName: Full=6-phosphogluconolactonase {ECO:0000313|EMBL:BAG44069.1}; EC=3.1.1.31 {ECO:0000313|EMBL:BAG44069.1};
- UniProt sequence Q39EM3: SubName: Full=3-carboxymuconate cyclase-like protein {ECO:0000313|EMBL:ABB09093.1};
- UniProt sequence Q881W7: SubName: Full=Uncharacterized protein {ECO:0000313|EMBL:AAO56265.1};
- UniProt sequence Q88NN7: SubName: Full=Gluconolactonase {ECO:0000313|EMBL:AAN66794.1}; EC=3.1.1.- {ECO:0000313|EMBL:AAN66794.1}; EC=3.1.1.17 {ECO:0000313|EMBL:AAN66794.1};
- Ignore hits to GFF3393 when looking for 'other' hits (galactaro-1,5-lactonase)
- Comment: 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.
- Total: 7 characterized proteins
gudD: D-glucarate dehydratase
uxaC: D-glucuronate isomerase
uxuB: D-mannonate dehydrogenase
uxuA: D-mannonate dehydratase
- Curated proteins or TIGRFams with EC 4.2.1.8
- Ignore hits to A4WA78 when looking for 'other' hits (D-galactonate dehydratase family member Ent638_1932; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to A5KUH4 when looking for 'other' hits (D-galactonate dehydratase family member VSWAT3_13707)
- Ignore hits to A6AMN2 when looking for 'other' hits (D-galactonate dehydratase family member A1Q3065)
- Ignore hits to A6M2W4 when looking for 'other' hits (D-galactonate dehydratase family member Cbei_4837)
- Ignore hits to A6VRA1 when looking for 'other' hits (D-galactonate dehydratase family member Mmwyl1_0037; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to A8RQK7 when looking for 'other' hits (D-galactonate dehydratase family member CLOBOL_02770)
- Ignore hits to B1ELW6 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B3PDB1 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B5GCP6 when looking for 'other' hits (D-galactonate dehydratase family member SSBG_02010)
- Ignore hits to B5QBD4 when looking for 'other' hits (D-galactonate dehydratase family member SeV_A0456; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to B5R541 when looking for 'other' hits (D-galactonate dehydratase family member SEN1436; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to B5RAG0 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to B8HCK2 when looking for 'other' hits (D-galactonate dehydratase family member Achl_0790)
- Ignore hits to C6CBG9 when looking for 'other' hits (D-galactonate dehydratase family member Dd703_0947; D-gluconate dehydratase; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to C6CVY9 when looking for 'other' hits (D-galactonate dehydratase family member Pjdr2_1176)
- Ignore hits to C6D9S0 when looking for 'other' hits (D-galactonate dehydratase family member PC1_0802; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to C6DI84 when looking for 'other' hits (D-galactonate dehydratase family member PC1_4063)
- Ignore hits to C7PW26 when looking for 'other' hits (D-galactonate dehydratase family member Caci_4410)
- Ignore hits to C8ZZN2 when looking for 'other' hits (D-galactonate dehydratase family member EGBG_01401)
- Ignore hits to C9A1P5 when looking for 'other' hits (D-galactonate dehydratase family member EGBG_02030)
- Ignore hits to C9CN91 when looking for 'other' hits (D-galactonate dehydratase family member ECAG_02205)
- Ignore hits to C9NUM5 when looking for 'other' hits (D-galactonate dehydratase family member VIC002985)
- Ignore hits to C9Y5D5 when looking for 'other' hits (D-galactonate dehydratase family member Ctu_1p00430)
- Ignore hits to D0KC90 when looking for 'other' hits (D-galactonate dehydratase family member Pecwa_4254)
- Ignore hits to D0X4R4 when looking for 'other' hits (D-galactonate dehydratase family member VME_00770)
- Ignore hits to D4GJ14 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-gluconate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to D7BPX0 when looking for 'other' hits (D-galactonate dehydratase family member SBI_01856; D-gluconate dehydratase; EC 4.2.1.-; EC 4.2.1.39)
- Ignore hits to D8ADB5 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to D9UNB2 when looking for 'other' hits (D-galactonate dehydratase family member SSLG_02014; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.8)
- Ignore hits to E1V4Y0 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-gluconate dehydratase; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to Q1QT89 when looking for 'other' hits (D-galactonate dehydratase family member ManD; D-gluconate dehydratase; D-mannonate dehydratase; EC 4.2.1.-; EC 4.2.1.39; EC 4.2.1.8)
- Ignore hits to Q2CIN0 when looking for 'other' hits (D-galactonate dehydratase family member OG2516_05608)
- Ignore hits to Q6DAR4 when looking for 'other' hits (D-galactonate dehydratase family member ECA0189)
- Ignore hits to Q8FHC7 when looking for 'other' hits (D-galactonate dehydratase family member RspA; D-mannonate dehydratase; Starvation sensing protein RspA homolog; EC 4.2.1.-; EC 4.2.1.8)
- Comment: Many proteins are annotated in SwissProt as "D-galactonate dehydratase family member" but have little activity on D-mannonoate; it is probably not the physiological substrate
- Total: 1 HMMs and 12 characterized proteins
kdgK: 2-keto-3-deoxygluconate kinase
- Curated proteins or TIGRFams with EC 2.7.1.45
- Curated proteins or TIGRFams with EC 2.7.1.178
- Ignore hits to Q9ZU29 when looking for 'other' hits (2-dehydro-3-deoxyglucono/galactono-kinase (EC 2.7.1.178))
- Ignore hits to DEHYDDEOXGALACTKIN-MONOMER when looking for 'other' hits (2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178; EC 2.7.1.58). 2-dehydro-3-deoxygalactonokinase (EC 2.7.1.178))
- Comment: The entry for Q9ZU29 is erroneous (the correct accession is Q97U29). EcoCyc 2-dehydro-3-deoxygalactonokinase (dgoK) is given this EC number as well but I could not determine why. It doesn't link to the ketodeoxygluconate kinase reaction.
- Total: 14 characterized proteins
eda: 2-keto-3-deoxygluconate 6-phosphate aldolase
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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