As text, or see rules and steps
# 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
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:
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:
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