As text, or see rules and steps
# Galacturonate utilization in GapMind is based on MetaCyc pathways # D-galacturonate degradation I via tagaturonate (metacyc:GALACTUROCAT-PWY), # pathway II via oxidation to 5-dehydro-4-deoxy-glucarate (metacyc:PWY-6486), # and another oxidative pathway (PMID:30249705). # Pathway III via galactonate (metacyc:PWY-6491) is reported only in fungi # and is not included in GapMind. # BT4105 (Q8A0B6), CA265_RS19855 (A0A1X9Z948), Pf1N1B4_5129 (A0A166QG26), and HSERO_RS23010 (D8IX31) are related # proteins with specific phenotypes on D-galacturonate exuT D-galacturonate transporter ExuT curated:SwissProt::P0AA78 curated:TCDB::P0AA78 curated:TCDB::P94774 uniprot:Q8A0B6 uniprot:A0A1X9Z948 uniprot:A0A166QG26 uniprot:D8IX31 # Transporters were identified using # query: transporter:galacturonate:D-galacturonate:galaturonate:D-galaturonate:D-galactopyranuronate:CPD-12523:CPD-12524:CPD-15633 galacturonate-transport: exuT gatA D-galacturonate transporter gatA curated:TCDB::A2R3H2 galacturonate-transport: gatA PS417_04205 D-galacturonate transporter curated:reanno::WCS417:GFF828 galacturonate-transport: PS417_04205 uxaC D-galacturonate isomerase EC:5.3.1.12 uxaB tagaturonate reductase EC:1.1.1.58 uxaA D-altronate dehydratase EC:4.2.1.7 # 2-keto-3-deoxygluconate kinase and 2-keto-3-deoxygluconate 6-phosphate aldolase import glucosamine.steps:kdgK import glucose.steps:eda # Pathway I begins with isomerization to # tagaturonate (a keto sugar) by uxaC. all: galacturonate-transport uxaC uxaB uxaA kdgK eda udh D-galacturonate dehydrogenase EC:1.1.1.203 gli D-galactarolactone isomerase EC:5.4.1.4 # BRENDA misannotates gli as gci gci D-galactarolactone cycloisomerase EC:5.5.1.27 ignore:BRENDA::A9CEQ7 kdgD 5-dehydro-4-deoxyglucarate dehydratase EC:4.2.1.41 import xylose.steps:dopDH # 2,5-dioxopentanonate dehydrogenase # Pathway II begins with oxidation to galactaro-1,5-lactone by udh, isomerization to the 1,4-lactone by gli, # and isomerization to 5-keto-4-deoxyglucarate by gci. all: galacturonate-transport udh gli gci kdgD dopDH # Two families of D-galactaro-1,5-lactonase were described, uxuL and uxuF. # All of these proteins are active on D-glucaro-1,5-lactone as well, # although PSPTO_2765 is much more active on galactaro,1-5-lactone. # UxuL = Rpic_4446 PSPTO_1052 # UxuF = Bcep1808_2255 BMULJ_02167 Bcep18194_A5499 PSPTO_2765 # PS417_17365 (GFF3393) and HSERO_RS15795 were inferred from mutant phenotype uxuL D-galactaro-1,5-lactonase (UxuL or UxuF) uniprot:B2UIY8 uniprot:Q888H2 uniprot:A4JG52 uniprot:A0A0H3KPX2 uniprot:Q39EM3 uniprot:Q881W7 curated:reanno::WCS417:GFF3393 curated:reanno::HerbieS:HSERO_RS15795 # Q8EMJ9 is the D-threo-forming enzyme, and is misannotated in BRENDA garD meso-galactarate dehydratase (L-threo-forming) GarD EC:4.2.1.42 ignore:BRENDA::Q8EMJ9 # In another oxidative pathway, the 1,5-lactone is hydrolyzed by uxuL or uxuF giving meso-galactorate, # and then a dehydratase (garD) forms 5-keto-4-deoxyglucarate. # In both oxidative pathways, this is decarboxylated/dehydrated # to 2,5-dioxopentanonate and oxidized to 2-oxoglutarate. all: galacturonate-transport udh uxuL garD kdgD dopDH
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 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