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:
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