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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 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