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# Trehalose degradation is based on MetaCyc pathways # I via trehalose-6-phosphate hydrolase (metacyc:TREDEGLOW-PWY), # II via cytoplasmic trehalase (metacyc:PWY0-1182), # III via trehalose-6-phosphate phosphorylase (metacyc:PWY-2721), # IV via inverting trehalose phosphorylase (metacyc:PWY-2722), # V via trehalose phosphorylase (metacyc:PWY-2723), # VI via periplasmic trehalase (metacyc:PWY0-1466), # as well as trehalose degradation via 3-ketotrehalose (PMID:33657378). treB trehalose PTS system, EII-BC components TreB curated:BRENDA::P36672 curated:SwissProt::P39794 curated:TCDB::Q720G7 uniprot:A0A0N9WDQ5 uniprot:A0A1N7UR85 curated:BRENDA::A0A0H3F7X9 # Ignore a close homlog in Serratia (TC 4.A.3.2.5 / Q8L3C4) which is reported to be the II-A component, # and the homolog in Salmonella. Include E. coli crr and B. subtilis ptsG, gamP, or ptsA (PMC6148471). treEIIA N-acetylglucosamine phosphotransferase system, EII-A component (Crr/PtsG/YpqE/GamP) curated:TCDB::P20166 uniprot:P50829 curated:SwissProt::P39816 curated:CharProtDB::CH_088352 ignore:SwissProt::P0A283 ignore:TCDB::Q8L3C4 curated:reanno::WCS417:GFF4500 curated:reanno::pseudo3_N2E3:AO353_15995 # PTS systems form trehalose 6-phosphate. # E. coli has EII-BC treB; crr is the EII-A. # B. subtilis has EII-BC treP. PMC6148471 shows that ptsG is the predominant EII-A but gamP and ptsA also function. # Listeria monocytogenes has EII-BC; the EII-A is not known. # Pseudomonas simiae WCS417 and P. fluorescens FW300-N2E3 have similar systems # but only EII-A is annotated. In FW300-N2E3, AO353_15980 (A0A0N9WDQ5) is the II-BC protein. # In WCS417, PS417_23050 (A0A1N7UR85) is the II-BC protein. These are both similar to E. coli treB. trehalose-PTS: treEIIA treB # ABC transporters: # Sinorhizobium meliloti has two distantly related systems: trehalose-inducible thuEFGK # and sucrose-inducible aglEFGK # Systems similar to thuEFGK from Sinorhizobium meliloti # are also found in Thermotoga maritima, Thermus thermophilus and Thermococcus litoralis. # (The ATPase component in T. maritima is not described.) # Mycobacterium tuberculosis has a similar system with a diverged SBP. # A system similar to that from T. thermophilus, in Pyrococcus furiosus, also transports trehalose (PMC2685544). thuE trehalose ABC transporter, substrate-binding component ThuE curated:TCDB::G4FGN8 curated:TCDB::O51923 curated:TCDB::Q72H68 curated:TCDB::Q9R9Q7 curated:SwissProt::Q7LYW7 # (Removed Sulfolobus treT, which is related but is described separately) thuF trehalose ABC transporter, permease component 1 (ThuF) curated:SwissProt::O51924 curated:SwissProt::P9WG03 curated:TCDB::G4FGN7 curated:TCDB::O51924 curated:TCDB::Q72H67 curated:reanno::Smeli:SM_b20326 thuG trehalose ABC transporter, permease component 2 (ThuG) curated:SwissProt::Q7LYX6 curated:SwissProt::P9WG01 curated:TCDB::G4FGN6 curated:TCDB::Q72H66 curated:reanno::Smeli:SM_b20327 thuK trehalose ABC transporter, ATPase component ThuK curated:SwissProt::P9WQI3 curated:SwissProt::Q9YGA6 curated:TCDB::Q72L52 curated:TCDB::Q9R9Q4 curated:TCDB::Q9X103 # Transporters and PTS systems were identified using # query: transporter:trehalose:D-trehalose trehalose-transport: thuE thuF thuG thuK lpqY trehalose ABC transporter, substrate-binding lipoprotein component LpqY curated:SwissProt::P9WGU9 trehalose-transport: lpqY thuF thuG thuK # Thermotoga maritima also has TC 3.A.1.1.22 system with two different SBPs (malE1E2) and also malF1G1G2K # These are duplicated operons and probably either paralog will work with either SBP. # Only malE2 binds trehalose (PMC1064059). # The ATPase component (malK) is quite similar to thuK and was included in that definition malE2 trehalose ABC transporter, substrate-binding component MalE2 curated:TCDB::Q9S5Y1 malF1 trehalose ABC transporter, permease component 1 curated:TCDB::Q9X0T0 malG1 trehalose ABC transporter, permease component 2 (MalG1/MalG2) curated:BRENDA::Q9X0S9 curated:BRENDA::Q9X2F5 trehalose-transport: malE2 malF1 malG1 thuK # Streptococcus mutans malXFGK malF trehalose ABC transporter, permease component 1 (MalF) curated:TCDB::Q8DT27 malG trehalose ABC transporter, permease component 2 (MalG) curated:TCDB::Q8DT26 # The related ATPase msmK can substitute for malK (PMC2223742) malK trehalose ABC transporter, ATPase component MalK curated:TCDB::Q8DT25 curated:TCDB::Q00752 malX trehalose ABC transporter, substrate-binding component MalX curated:TCDB::Q8DT28 trehalose-transport: malF malG malK malX # Sulfolobus solfataricus treSTUV treS trehalose ABC transporter, substrate-binding comopnent TreS curated:TCDB::Q97ZC3 treT trehalose ABC transporter, permease component 1 (TreT) curated:TCDB::Q97ZC2 treU trehalose ABC transporter, permease component 2 (TreU) curated:TCDB::Q97ZC1 treV trehalose ABC transporter, ATPase component TreV curated:TCDB::Q97ZC0 trehalose-transport: treS treT treU treV # S. meliloti aglEFGK. # A similar system from Dinoroseobacter shibae, Dshi_1652:Dshi_1648, is involved in maltose uptake. # Dinoroseobacter shibae aglE = Dshi_1652 = A8LLL6. # Ignore similarity to Slr0529, which may also transport trehalose aglE trehalose ABC transporter, substrate-binding component AglE curated:TCDB::Q9Z3R5 uniprot:A8LLL6 ignore:TCDB::Q55471 # Dinoroseobacter shibae aglF = Dshi_1651 = A8LLL5. aglF trehalose ABC transporter, permease component 1 (AglF) curated:reanno::Smeli:SMc03062 uniprot:A8LLL5 # Dinoroseobacter shibae aglG = Dshi_1650 = A8LLL4. aglG trehalose ABC transporter, permease component 2 (AglG) curated:reanno::Smeli:SMc03063 uniprot:A8LLL4 # Dinoroseobacter shibae aglK = Dshi_1648 = A8LLL2. aglK trehalose ABC trehalose, ATPase component AglK curated:reanno::Smeli:SMc03065 uniprot:A8LLL2 trehalose-transport: aglE aglF aglG aglK # For the system in Bdellovibrio bacteriovorus, just one protein (fused MalEF) seems to have been studied, # and did not have access to the paper, so did not include. # Streptomyces coelicolor has agl3EFG; although expression is induced by trehalose, its function # remains uncertain, so it is not described here TRET1 facilitated trehalose transporter Tret1 curated:SwissProt::A5LGM7 curated:SwissProt::A9ZSY2 curated:SwissProt::A9ZSY3 curated:SwissProt::Q8MKK4 trehalose-transport: TRET1 # Tret1-1 has a very high Km so is not included import glucose.steps:glucose-utilization glk BT2158 periplasmic trehalose 3-dehydrogenase (BT2158) curated:reanno::Btheta:351686 # These gene names are from the homologous system in Caulobacter crescentus, which is required for # lactose utilization; but Caulobacter crescentus does not grow with trehalose as the sole # source of carbon, and Caulobacter LacACB may not be active on trehalsoe. lacA periplasmic trehalose 3-dehydrogenase, LacA subunit curated:reanno::Pedo557:CA265_RS15345 curated:reanno::Cola:Echvi_1847 ignore_other:1.1.99.13 lacC periplasmic trehalose 3-dehydrogenase, LacC subunit curated:reanno::Pedo557:CA265_RS15340 curated:reanno::Cola:Echvi_1848 ignore_other:1.1.99.13 lacB periplasmic trehalose 3-dehydrogenase, cytochrome c subunit (LacB) curated:reanno::Pedo557:CA265_RS15360 curated:reanno::Cola:Echvi_1841 ignore_other:1.1.99.13 trehalose-3-dehydrogenase: BT2158 trehalose-3-dehydrogenase: lacA lacC lacB # BT2157 (351686) is required for utilization of trehalose (or 3-ketotrehalose) and # hydrolyzes 3-ketotrehalose. CA265_RS22975 and Echvi_2921 are similar proteins that are # involved in trehalose utilization. klh 3-ketotrehalose hydrolase curated:reanno::Btheta:351685 curated:reanno::Pedo557:CA265_RS22975 curated:reanno::Cola:Echvi_2921 # In the 3-ketotrehalose pathway, a periplasmic dehydrogenase forms 3-ketotrehalose, # a periplasmic 3-ketoglycoside hydrolase (klh) forms glucose and 3-ketoglucose, # and the glucose is taken up and utilized; # the fate of the 3-ketoglucose is not well understood, but its utilization might not be necessary. all: trehalose-3-dehydrogenase klh glucose-utilization # PGA1_c07890 (I7EUW4) is important for trehalose and cellobiose utilization (it is probably cytoplasmic). # Dshi_1649 from Dinoroseobacter shibae (A8LLL3) is important for trehalose utilization. treF trehalase EC:3.2.1.28 uniprot:I7EUW4 uniprot:A8LLL3 # In pathway VI, a periplasmic trehalase forms glucose, which is utilized. all: treF glucose-utilization treC trehalose-6-phosphate hydrolase EC:3.2.1.93 # In pathway I, after uptake and phosphorylation by the PTS, # trehalose 6-phosphate hydrolase (treC) forms D-glucose 6-phosphate and D-glucose, # and glucokinase (glk) phosphorylates the glucose. all: trehalose-PTS treC glk # In pathway II, a cytoplasmic trehalase cleaves trehalose to two glucose, # followed by phosphorylation by glk. all: trehalose-transport treF glk trePP trehalose-6-phosphate phosphorylase EC:2.4.1.216 pgmB beta-phosphoglucomutase EC:5.4.2.6 # In pathway III, after uptake and phosphorylation by the PTS, # trehalose-6-phosphate phosphorylase (trePP) forms beta-glucose-1-phosphate and glucose-6-phosphate, # and beta-phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate. all: trehalose-PTS trePP pgmB # Forms beta-glucose 1-phosphate and glucose. # CA265_RS24655 is misannotated as a trehalose phosphorylase (the fitness data actually confirms # that it is a maltose phosphorylase). treP trehalose phosphorylase, inverting EC:2.4.1.64 ignore:reanno::Pedo557:CA265_RS24655 # In pathway IV, a secreted inverting trehalose phoshorylase (treP) forms beta-glucose 1-phosphate and glucose; # the beta-D-glucose is consumed by beta-phosphoglucomutase. all: trehalose-transport treP pgmB glk PsTP trehalose phosphorylase EC:2.4.1.231 import galactose.steps:pgmA # In pathway V, trehalose phosphorylase forms alpha-glucose-1-phosphate and glucose; # these are converted to glucose-6-P by alpha-phosphoglucomutase (pgmA) and glk. # (This is a fungal pathway and might not occur in prokaryotes.) all: trehalose-transport PsTP pgmA glk
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