Definition of D-mannitol catabolism
As rules and steps, or see full text
Rules
Overview: Mannitol degradation in GapMind is based on MetaCyc pathway mannitol degradation I via a phosphotransferase system (link), pathway II via mannitol 1-dehydrogenase (link), or another oxidative pathway with mannitol 2-dehydrogenase (PMID:8254318).
- all:
- mannitol-PTS and mtlD
- or mannitol-transport, mt1d, mak and manA
- or mannitol-transport, mt2d and scrK
- Comment: In pathway I, the phosphotransferase system forms mannitol 1-phosphate and 5-dehydrogenase (mtlD) forms fructose 6-phosphate. In pathway II, mannitol is oxidized to mannose by mt1d, phosphorylated to mannose 6-phosphate, and isomerized to fructose 6-phosphate. Alternatively, mannitol 2-dehydrogenase (mt2d) forms fructose, and fructokinase (scrK) forms fructose 6-phosphate.
- mannitol-transport:
- mtlE, mtlF, mtlG and mtlK
- or PLT5
- Comment: Transporters and PTS systems were identified using query: transporter:mannitol:D-mannitol
- mannitol-PTS:
Steps
mtlA: mannitol phosphotransferase system, EII-CBA components
- Curated sequence P00550: protein-Npi-phosphohistidine-D-mannitol phosphotransferase (EC 2.7.1.197). PTS system mannitol-specific EIICBA component; EC 2.7.1.-; EC 2.7.1.69. PTS system mannitol-specific EIICBA component; EIICBA-Mtl; EII-Mtl; EC 2.7.1.197. Mannitol porter (MtlA) (mannitol-1-P forming), the mannitol IICBA complex. mannitol-specific PTS enzyme IICBA component (EC 2.7.1.197; EC 2.7.1.198). mannitol-specific PTS enzyme IICBA component (EC 2.7.1.197; EC 2.7.1.198)
- Curated sequence Q9KKQ7: The mannitol/glucitol transporter, MtlA (IICBAMtl)
- Ignore hits to P42956 when looking for 'other' hits (PTS system, mannitol-specific IICBA component aka EIICBA-Mtl aka Mannitol-permease IIABC component aka Phosphotransferase enzyme II, CBA component aka EC 2.7.1.69 aka EII-Mtl, component of The mannitol porter (MtlA) (mannitol-1-P forming), MtlAF)
- Ignore hits to P50852 when looking for 'other' hits (PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197)
- Ignore hits to O65989 when looking for 'other' hits (PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197)
- Ignore hits to P69826 when looking for 'other' hits (PTS system mannitol-specific cryptic EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197. EIICB-Mtl. mannitol-specific PTS enzyme IICB component CmtA (EC 2.7.1.197). mannitol-specific PTS enzyme IICB component CmtA (EC 2.7.1.197))
- Ignore hits to P28008 when looking for 'other' hits (PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197)
- Comment: Unified EII-CBA in Escherichia coli (mtlA) and Vibrio cholerae. Ignore similarity to the II-CB only systems.
- Total: 2 characterized proteins
cmtA: mannitol phosphotransferase system, EII-CB component CmtA/MtlF
- Curated sequence P69826: PTS system mannitol-specific cryptic EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197. EIICB-Mtl. mannitol-specific PTS enzyme IICB component CmtA (EC 2.7.1.197). mannitol-specific PTS enzyme IICB component CmtA (EC 2.7.1.197)
- Curated sequence P42956: PTS system, mannitol-specific IICBA component aka EIICBA-Mtl aka Mannitol-permease IIABC component aka Phosphotransferase enzyme II, CBA component aka EC 2.7.1.69 aka EII-Mtl, component of The mannitol porter (MtlA) (mannitol-1-P forming), MtlAF
- Curated sequence P28008: PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197
- Curated sequence O65989: PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197
- Curated sequence P50852: PTS system mannitol-specific EIICB component; EIICB-Mtl; EII-Mtl; EC 2.7.1.197
- Ignore hits to P00550 when looking for 'other' hits (protein-Npi-phosphohistidine-D-mannitol phosphotransferase (EC 2.7.1.197). PTS system mannitol-specific EIICBA component; EC 2.7.1.-; EC 2.7.1.69. PTS system mannitol-specific EIICBA component; EIICBA-Mtl; EII-Mtl; EC 2.7.1.197. Mannitol porter (MtlA) (mannitol-1-P forming), the mannitol IICBA complex. mannitol-specific PTS enzyme IICBA component (EC 2.7.1.197; EC 2.7.1.198). mannitol-specific PTS enzyme IICBA component (EC 2.7.1.197; EC 2.7.1.198))
- Ignore hits to Q9KKQ7 when looking for 'other' hits (The mannitol/glucitol transporter, MtlA (IICBAMtl))
- Comment: Two-part PTS, with EII-CB (cmtA/mtlA) separate from EII-A (cmtB/mtlF), in Escherichia coli (cmt system), Bacillus subtilis, Staphylococcus carnosus, Clostridium acetobutylicum, and Geobacillus stearothermophilus. Ignore similarity to the unified systems.
- Total: 5 characterized proteins
cmtB: mannitol phosphotransferase system, EII-A component CmtB/MtlF
- Curated sequence CMTB-MONOMER: mannitol-specific PTS enzyme IIA component CmtB (EC 2.7.1.197). mannitol-specific PTS enzyme IIA component CmtB (EC 2.7.1.197)
- Curated sequence P17876: Mannitol-specific phosphotransferase enzyme IIA component; EIIA; EIII; PTS system mannitol-specific EIIA component
- Curated sequence C0H3V2: Mannitol-specific phosphotransferase enzyme IIA component, component of The mannitol porter (MtlA) (mannitol-1-P forming), MtlAF
- UniProt sequence O65991: SubName: Full=MtlF {ECO:0000313|EMBL:AAC12850.1};
- UniProt sequence Q45420: RecName: Full=Mannitol-specific phosphotransferase enzyme IIA component {ECO:0000250|UniProtKB:P0A0E0}; AltName: Full=EIIA {ECO:0000250|UniProtKB:P0A0E0}; AltName: Full=EIII {ECO:0000303|PubMed:8824601}; AltName: Full=PTS system mannitol-specific EIIA component {ECO:0000250|UniProtKB:P0A0E0};
- Ignore hits to P0A0E0 when looking for 'other' hits (Mannitol-specific phosphotransferase enzyme IIA component; EIIA; EIII; PTS system mannitol-specific EIIA component)
- Comment: For C. acetobutylicum, the mtlF component is is O65991 (see PMID:11160802); and in Geobacillus it is Q45420 (PMID:824601; Genbank U18943.1). There is also a paper about the EII-A and EII-BC system from S. aureus, see PMID:3064811 and SwissProt P0A0E0, but I'm not sure this is the correct accession, so ignore it.
- Total: 5 characterized proteins
gutB: mannitol PTS system, EII-A component GutB
- Curated sequence CH_090883: PTS system, glucitol/sorbitol-specific, IIA component. PTS system glucitol/sorbitol-specific EIIA component; EIIA-Gut; EIII-Gut; Glucitol/sorbitol-specific phosphotransferase enzyme IIA component. PTHA aka SRLB aka GUTB aka B2704, component of Glucitol porter. sorbitol-specific PTS enzyme IIA component (EC 2.7.1.198; EC 2.7.1.197). sorbitol-specific PTS enzyme IIA component (EC 2.7.1.198; EC 2.7.1.197)
- Comment: EII-A, EII-BC1, and EII-C2 -- the sorbitol/glucitol system in E. coli, which also transports mannitol.
- Total: 1 characterized proteins
gutE: mannitol PTS system, EII-BC1 component GutE
- Curated sequence P56580: PTS system glucitol/sorbitol-specific EIIB component; EII-Gut; Enzyme II-Gut; Glucitol/sorbitol-specific phosphotransferase enzyme IIB component; EC 2.7.1.198. PTHB aka SRLE aka GUTE aka B2703, component of Glucitol porter. sorbitol-specific PTS enzyme IIBC1 component (EC 2.7.1.198; EC 2.7.1.197). sorbitol-specific PTS enzyme IIBC1 component (EC 2.7.1.198; EC 2.7.1.197)
- Ignore hits to O32522 when looking for 'other' hits (PTS system glucitol/sorbitol-specific EIIB component; EII-Gut; Enzyme II-Gut; Glucitol/sorbitol-specific phosphotransferase enzyme IIB component; EC 2.7.1.198)
- Comment: Ignore similarity to close homolog in Erwinia, annotated as transporting sorbitol only
- Total: 1 characterized proteins
gutA: mannitol PTS system, EII-C2 component GutA
- Curated sequence P56579: PTS system glucitol/sorbitol-specific EIIC component; EIIC-Gut; Glucitol/sorbitol permease IIC component. PTHC aka SRLA aka GUTA aka SBL aka B2702, component of Glucitol porter. sorbitol-specific PTS enzyme IIC2 component (EC 2.7.1.198; EC 2.7.1.197). sorbitol-specific PTS enzyme IIC2 component (EC 2.7.1.198; EC 2.7.1.197)
- Ignore hits to O32521 when looking for 'other' hits (PTS system glucitol/sorbitol-specific EIIC component; EIIC-Gut; Glucitol/sorbitol permease IIC component)
- Comment: Ignore similarity to close homolog in Erwinia, annotated as transporting sorbitol only
- Total: 1 characterized proteins
mtlE: polyol ABC transporter, substrate-binding component MtlE/SmoE
- Curated sequence O30491: MtlE, component of The polyol (mannitol, glucitol (sorbitol), arabitol (arabinitol; lyxitol)) uptake porter, MtlEFGK
- Curated sequence GFF2493: ABC transporter for D-Mannitol, D-Mannose, and D-Sorbitol, periplasmic substrate-binding protein
- Curated sequence PfGW456L13_3042: ABC transporter for D-Mannitol, D-Mannose, and D-Mannose, periplasmic substrate-binding component
- Curated sequence AO353_25880: ABC transporter for D-mannitol and D-mannose, periplasmic substrate-binding component
- Ignore hits to AO356_00025 when looking for 'other' hits (ABC transporter for D-Sorbitol, periplasmic substrate-binding component)
- Ignore hits to Pf6N2E2_1963 when looking for 'other' hits (ABC transporter for D-sorbitol, periplasmic substrate-binding component)
- Curated sequence O30831: SmoE, component of Hexitol (glucitol; mannitol) porter
- Comment: MtlEFGK in several strains of Pseudomonas fluorescens or Pseudomonas simiae, or smoEFGK in Rhodopseudomonas sphaeroides. (The Rhodopseudomonas system was missed by the query; it is annotated as a hexitol transporter.) For all components, ignore simlarity to close homologs in FW300-N2C3 or FW300-N2E2, annotated as transporting sorbitol only.
- Total: 5 characterized proteins
mtlF: polyol ABC transporter, permease component 1 (MtlF/SmoF)
- Curated sequence O30492: MtlF, component of The polyol (mannitol, glucitol (sorbitol), arabitol (arabinitol; lyxitol)) uptake porter, MtlEFGK
- Curated sequence GFF2492: ABC transporter for D-Mannitol, D-Mannose, and D-Sorbitol, permease component 2
- Curated sequence PfGW456L13_3041: ABC transporter for D-Mannitol, D-Mannose, and D-Mannose, permease component 2
- Curated sequence AO353_25885: ABC transporter for D-mannitol and D-mannose, permease component 1
- Ignore hits to AO356_00020 when looking for 'other' hits (ABC transporter for D-Sorbitol, permease component 2)
- Ignore hits to Pf6N2E2_1962 when looking for 'other' hits (ABC transporter for D-sorbitol, permease component 1)
- Curated sequence O30832: SmoF, component of Hexitol (glucitol; mannitol) porter
- Total: 5 characterized proteins
mtlG: polyol ABC transporter, permease component 2 (MtlG/SmoG)
- Curated sequence O30493: MtlG, component of The polyol (mannitol, glucitol (sorbitol), arabitol (arabinitol; lyxitol)) uptake porter, MtlEFGK
- Curated sequence GFF2491: ABC transporter for D-Mannitol, D-Mannose, and D-Sorbitol, permease component 1
- Curated sequence PfGW456L13_3040: ABC transporter for D-Mannitol, D-Mannose, and D-Mannose, permease component 1
- Curated sequence AO353_25890: ABC transporter for D-mannitol and D-mannose, permease component 2
- Ignore hits to Pf6N2E2_1961 when looking for 'other' hits (ABC transporter for D-sorbitol, permease component 2)
- Ignore hits to AO356_00015 when looking for 'other' hits (ABC transporter for D-Sorbitol, permease component 1)
- Curated sequence O30833: SmoG, component of Hexitol (glucitol; mannitol) porter
- Total: 5 characterized proteins
mtlK: polyol ABC transporter, ATP component MtlK/SmoG
- Curated sequence O30494: MtlK, component of The polyol (mannitol, glucitol (sorbitol), arabitol (arabinitol; lyxitol)) uptake porter, MtlEFGK
- Curated sequence GFF2490: ABC transporter for D-Mannitol, D-Mannose, and D-Sorbitol, ATPase component
- Curated sequence PfGW456L13_3039: ABC transporter for D-Mannitol, D-Mannose, and D-Mannose, ATPase component
- Curated sequence AO353_25895: ABC transporter for D-mannitol and D-mannose, ATPase component
- Ignore hits to Pf6N2E2_1960 when looking for 'other' hits (ABC transporter for D-sorbitol, ATPase component)
- Ignore hits to AO356_00010 when looking for 'other' hits (ABC transporter for D-Sorbitol, ATPase component)
- Curated sequence P54933: SmoK aka POLK, component of Hexitol (glucitol; mannitol) porter
- Total: 5 characterized proteins
PLT5: polyol transporter PLT5
- Curated sequence CH_091483: polyol transporter 5. Polyol transporter 5; Protein POLYOL TRANSPORTER 5; AtPLT5; Sugar-proton symporter PLT5. The broad specificity sugar/sugar alcohol (myo-inositol, glycerol, ribose, sorbitol, mannitol, xylitol, erythritol, etc) H+ symporter, AtPLT5 (transports a wide range of hexoses, pentoses, tetroses, sugar alcohols and a sugar acid, but not disaccharides) (Reinders et al., 2005) (expressed in roots, leaves and floral organs)
- Total: 1 characterized proteins
mtlD: mannitol-1-phosphate 5-dehydrogenase
mt1d: mannitol 1-dehydrogenase
mak: mannose kinase
manA: mannose-6-phosphate isomerase
- Curated proteins or TIGRFams with EC 5.3.1.8
- UniProt sequence P29954: RecName: Full=Mannose-6-phosphate isomerase; EC=5.3.1.8; AltName: Full=Phosphohexomutase; AltName: Full=Phosphomannose isomerase; Short=PMI;
- Comment: SMc03111 (P29954) is specifically important for utilizing mannose, which confirms it is mannose 6-phosphate isomerase
- Total: 1 HMMs and 29 characterized proteins
mt2d: mannitol 2-dehydrogenase
scrK: fructokinase
- Curated proteins or TIGRFams with EC 2.7.1.4
- Ignore hits to Q09123 when looking for 'other' hits (Fructokinase; EC 2.7.1.4)
- Comment: ignore fragmentary sequence of Q09123
- Total: 36 characterized proteins
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About GapMind
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:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
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:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
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