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# Xylose degradation in GapMind is based on MetaCyc pathways # I via D-xylulose (metacyc:XYLCAT-PWY), # II via xylitol (metacyc:PWY-5516), # III or V via 2-dehydro-3-deoxy-D-arabinonate (DKDP) dehydratase (metacyc:PWY-6760, metacyc:PWY-8020), # IV via DKDP aldolase (metacyc:PWY-7294), # as well as another pathway via DKDP dehydrogenase (PMC6336799). # monomeric transporters include xylT-like proteins, and also Gal2, GlcP, but not XYLP_LACPE # TCDB also mentions MA6T (TC 2.A.1.1.10; P15685) but I did not find a reference linking this to xylose uptake # Fitness data identified CCNA_00857 (CC0814; A0A0H3C6H3) as the xylose transporter in Caulobacter crescentus, # consistent with a previous report (PMC2168598). xylT D-xylose transporter curated:SwissProt::O52733 curated:CharProtDB::CH_091400 curated:CharProtDB::CH_091493 curated:CharProtDB::CH_109760 curated:SwissProt::P0AE24 curated:SwissProt::P96710 curated:TCDB::C4B4V9 curated:TCDB::Q0WWW9 curated:TCDB::Q2MDH1 curated:TCDB::Q2MEV7 curated:TCDB::Q64L87 curated:TCDB::Q9XIH7 uniprot:A0A0H3C6H3 gal2 galactose/glucose/xylose uniporter curated:CharProtDB::CH_091029 glcP glucose/mannose/xylose:H+ symporter curated:SwissProt::O07563 # Echvi_1871 (L0FZF3) seems to be a xylose transporter as well as a glucose/galactose transporter. Echvi_1871 sodium/xylose cotransporter uniprot:L0FZF3 # ABC transporters include xylFGH from several organisms (T. maritima has a diverged SBP), # another system from T. maritima (xylE_Tm xylF_Tm XylK_Tm), # and araVUTS from Sulfolobus solfataricus # T. maritima has a diverged SBP, Tmari_1858 (uniprot:G4FGN5). # Tmari_1858 is sometimes annotated as gluE, and is glucose induced. # But the Km for xylose is quite low, so, considered it a xylose transporter as well. # Ignore P54083 (sbpA from A. brasilensis), not known if it transports xylose or not; # close homolog HSERO_RS05190 is mildly important for fitness during growth on xylose, so, it may transport xylose. xylF ABC transporter for xylose, substrate binding component xylF curated:CharProtDB::CH_003787 curated:TCDB::A6LW10 curated:TCDB::P25548 curated:TCDB::G4FGN5 ignore:SwissProt::P54083 xylG ABC transporter for xylose, ATP-binding component xylG curated:SwissProt::P37388 curated:TCDB::A6LW11 curated:TCDB::G4FGN3 curated:TCDB::O05176 xylH ABC transporter for xylose, permease component xylH curated:TCDB::A6LW12 curated:CharProtDB::CH_024441 curated:TCDB::G4FGN4 curated:TCDB::O05177 # The ABC transporter in T. maritima described above is TC 3.A.1.2.20. # TC 3.A.1.2.18 describes another ABC transporter for xylose in T. maritima: # Q9WXW7 = TM0112 = XylF, the permease subunit; # Q9WXW9 = TM0114 = XylE, the SBP, reported high affinity for xylose (PMC1392961); # Q9WXX0 = TM0115 = xylK is the ATPase-binding component. # Also TM0113 is a putative xylanase. # (Only the SBP seems to be characterized but the clustering of these genes with each other # and other xylose-related genes is quite suggestive.) # TC 3.A.1.2.18 also includes Q9WXW0 = TM0105, for which TCDB cites Nanavati et al (PMC1392961), # but that paper does not mention this gene. Probably a curation error. xylF_Tm ABC transporter for xylose, permease component xylF curated:TCDB::Q9WXW7 xylE_Tm ABC transporter for xylose, substrate binding component xylE uniprot:Q9WXW9 xylK_Tm ABC transporter for xylose, ATP binding component xylK uniprot:Q9WXX0 # AraVUTS (TC 3.A.1.1.14) from Sulfolobus solfataricus araV component of Arabinose, fructose, xylose porter curated:TCDB::Q97UF2 araU component of Arabinose, fructose, xylose porter curated:TCDB::Q97UF3 araT component of Arabinose, fructose, xylose porter curated:TCDB::Q97UF4 araS component of Arabinose, fructose, xylose porter curated:TCDB::Q97UF5 # GtsABCD from P. fluorescens WCS417 (PS417_22130:PS417_22145) is very important for utilization # of both glycose and xylose. # Similar systems in other Pseudomonas have been reported as glucose transporters. # In P. putida, after enzymes for xylose catabolism were introduced and the strain was # evolved for growth on xylose, GtsABCD were required for xylose utilization, although there were # two point mutations in GtsA, so it is not certain if the wild-type P. putida GtsA binds xylose # efficiently (see PMC3340264). The P. putida system is marked ignore. # GtsA = PS417_22145 = GFF4324 gtsA xylose ABC transporter, periplasmic substrate-binding component GtsA curated:reanno::WCS417:GFF4324 ignore:TCDB::Q88P38 # GtsB = PS417_22140 = GFF4323 gtsB xylose ABC transporter, permease component 1 GtsB curated:reanno::WCS417:GFF4323 ignore:TCDB::Q88P37 # GtsC = PS417_22135 = GFF4322 gtsC xylose ABC transporter, permease component 2 GtsC curated:reanno::WCS417:GFF4322 ignore:TCDB::Q88P36 # GtsD = PS417_22130 = GFF4321 gtsD xylose ABC transporter, ATPase component GtsD curated:reanno::WCS417:GFF4321 ignore:TCDB::Q88P35 # Transporters were identified using # query: transporter:D-xylose:xylose:CPD-15377 xylose-transport: xylT xylose-transport: gal2 xylose-transport: glcP xylose-transport: Echvi_1871 xylose-transport: xylF xylG xylH xylose-transport: xylF_Tm xylE_Tm xylK_Tm xylose-transport: araV araU araT araS xylose-transport: gtsA gtsB gtsC gtsD # There are also reports of xylose uptake by the mannose PTS system in Lactobacillus # (S. Chaillou et al, J. Bact. 1999) but with poor affinity. xylA xylose isomerase EC:5.3.1.5 # Echvi_1875 (L0FZT0) is annotated as xylulose kinase and has its strongest phentoypes on xylose. # CA_C2612 (Q97FW4) from Clostridium acetobutylicum was proven to be xylulose kinase (PMC2873477). # BT0792 (Q8A9M3) has its strongest phenotypes on xylose. xylB xylulokinase EC:2.7.1.17 uniprot:L0FZT0 uniprot:Q97FW4 uniprot:Q8A9M3 #rpe ribulose-phosphate epimerase EC:5.1.3.1 #rpi ribose-5-phosphate isomerase EC:5.3.1.6 xyrA xylitol reductase EC:1.1.1.307 # L-iditol 2-dehydrogenases (EC:1.1.1.14) often act on xylitol as well, so are ignored. # There's also some xylulose reductases annotated but without an EC number. xdhA xylitol dehydrogenase EC:1.1.1.9 ignore_other:1.1.1.14 ignore_other:xylulose reductase # Watanabe et al 2019 (PMC6336799) show that # C785_RS00860 = WP_034330287.1 = A0A4R8NY47 is D-xylose dehydrogenase (xdh). # Another issue is that xdh from Haloferax volcanii (HVO_B0028; D4GP29) is reported to form xylono-1,4-lactone, # (Sutter et al 2017, PMID:28854683), but this is not reflected in the databases, # and for some (many?) xylose dehydrogenases, # it is uncertain which lactone they form. # So, both forms of D-xylose dehydrogenase are included in "xdh." xdh D-xylose dehydrogenase EC:1.1.1.179 EC:1.1.1.175 uniprot:A0A4R8NY47 # EC:3.1.1.110 is the 1,5-lactonase; EC:3.1.1.68 is the 1,4-lactonase; # both are included in "xylC." # xylono-1,4-lactonase is sometimes given EC:3.1.1.15 (L-arabinino-1,4-lactonase) so ignore those; # indeed HVO_B0030 = metacyc::MONOMER-20630 has both 1,4-lactonase activities (PMID:28854683). xylC xylonolactonase EC:3.1.1.110 EC:3.1.1.68 ignore_other:3.1.1.15 # Watanabe et al (PMC6336799) show that # C785_RS00855 = WP_039783171.1 = UPI0004007277 is D-xylonate dehydratase (xad); # this is 98% identical to D8IWS7_HERSS, so use that identifier. xad D-xylonate dehydratase EC:4.2.1.82 uniprot:D8IWS7_HERSS # Watanabe et al (PMC6336799) show that # C785_RS13680 = WP_039786859.1 = UPI00041852D2 is DKDP dehydratase (kdaD). # Is 98% identical to HSERO_RS19360, which is included via reannotations. kdaD 2-keto-3-deoxy-D-arabinonate dehydratase EC:4.2.1.141 dopDH 2,5-dioxopentanonate dehydrogenase EC:1.2.1.26 # A number of EC:4.1.2.55 enzymes are similar but are promiscuous and are likely # to have this activity as well. This includes uniprot:Q97U28 which is nearly identical to the # promiscuous uniprot:KDGA_SACSO (O54288), but is not annotated with this activity. DKDP-aldolase 2-dehydro-3-deoxy-D-arabinonate aldolase EC:4.1.2.28 ignore_other:4.1.2.55 # glycolaldehyde oxidoreductase has multiple subunits and no EC number (uniprot:Q97VI4, uniprot:Q97VI7, uniprot:Q97VI6). # This is an inference from close homologs from S. acidocaldarius, which # have demonstrated activity on glyceraldehyde-3-phosphate, glyceraldehyde, and acetaldehyde, but not # on glycolaldehyde itself, so there's no proof that these genes provide the activity. # Related enzymes in EC:1.2.99.8 are promiscuous, may well have this activity, so ignore. aldox-large (glycol)aldehyde oxidoreductase, large subunit curated:metacyc::MONOMER-18071 curated:SwissProt::Q4J6M3 ignore_other:1.2.99.8 aldox-med (glycol)aldehyde oxidoreductase, medium subunit curated:metacyc::MONOMER-18072 curated:SwissProt::Q4J6M6 ignore_other:1.2.99.8 aldox-small (glycol)aldehyde oxidoreductase, small subunit curated:metacyc::MONOMER-18073 curated:SwissProt::Q4J6M5 ignore_other:1.2.99.8 # There's also glycolaldehyde dehydrogenase, EC:1.2.1.21 (aldA), with a single subunit aldA (glycol)aldehyde dehydrogenase EC:1.2.1.21 # The NADP based glyoxylate reductase (EC:1.1.1.79) is probably biased in the wrong direction # for glycolate oxidation, so do not include, but ignore homology to it. gyaR glyoxylate reductase EC:1.1.1.26 ignore_other:1.1.1.79 glycolaldehyde-dehydrogenase: aldA glycolaldehyde-dehydrogenase: aldox-large aldox-med aldox-small # Besides the standard enzyme, there's an archaeal enzyme that is sometimes annotated as EC:4.1.3.24, # but that only includes the formation of malyl-CoA, not the cleavage to malate. glcB malate synthase EC:2.3.3.9 ignore_other:4.1.3.24 # C785_RS13675 = WP_039786858.1 = A0A4P7ABK7 is the DKDP 4-dehydrogenase (PMC6336799). DKDP-dehydrog D-2-keto-3-deoxypentoate dehydrogenase uniprot:A0A4P7ABK7 # C785_RS20550 = WP_039788920.1 = A0A2E7P912 is the HDOP hydrolase (PMC6336799). # This enzyme is also similar to SM_b21112, thought to be L-2,4-diketo-3-deoxyrhamnonate hydrolase # and 2,4-dioxopentanoate hydrolase; it is plausible that SM_b21112 acts on HDOP as well. # Similarly for BPHYT_RS34210 (thought to act on 2,4-diketo-3-deoxy-L-fuconate = L-2,4-diketo-3-deoxyrhamnonate). # Both of these homologs are ignored. HDOP-hydrol 5-hydroxy-2,4-dioxopentanonate hydrolase uniprot:A0A2E7P912 ignore:reanno::BFirm:BPHYT_RS34210 ignore:reanno::Smeli:SM_b21112 # In pathway I, isomerase xylA forms D-xylulose and kinase # xylB forms D-xylulose 5-phosphate, an intermediate in the pentose phosphate pathway. all: xylose-transport xylA xylB # In pathway II, the reductase xyrA forms xylitol, the dehydrogenase xdhA forms xylitol, # and the kinase xylB forms D-xylulose 5-phosphate. (This pathway is only reported in fungi.) all: xylose-transport xyrA xdhA xylB # In pathway III or V, dehydrogenase xdh forms xylonolactone, lactonase xylC forms D-xylonate, # dehydratase xad forms 2-dehydro-3-deoxy-D-arabinonate, # dehydratase kdaD forms 2,5-dioxopentanoate (also known as α-ketoglutarate semialdehyde), and # dopDH forms 2-oxoglutarate, an intermediate in the TCA cycle. # (Pathway III has a 1,4-lactone intermediate, while pathway V has a 1,5-lactone intermediate; # GapMind does not distinguish these.) all: xylose-transport xdh xylC xad kdaD dopDH # In pathway IV, xdh and xylC form D-xylonate, dehydratase xad forms 2-dehydro-3-deoxy-D-arabinonate (DKDP), # and an aldolase forms pyruvate and glycolaldehyde; glycolaldehyde is oxidized to glycolate and to glyoxylate, # and assimilated by malate synthase (glcB). all: xylose-transport xdh xylC xad DKDP-aldolase glycolaldehyde-dehydrogenase gyaR glcB # Alternatively, after DKDP is formed, # a dehydrogenase forms 5-hydroxy,2-4-dioxopentanonate (HDOP), # and a hydrolase forms pyruvate and glycolate (PMC6336799); # the glycolate is oxidized to glyoxylate and converted to malate. all: xylose-transport xdh xylC xad DKDP-dehydrog HDOP-hydrol gyaR glcB
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