As text, or see rules and steps
# Myo-inositol degradation in GapMind is based on MetaCyc pathways # myo-inositol degradation I via inosose dehydratase (metacyc:P562-PWY) # and pathway II inosose dehydrogenase (metacyc:PWY-7241). # ABC transporters have been described in # Caulobacter crescentus, Phaeobacter inhibens, Pseudomonas simiae, and Pseudomonas fluorescens PGA1_c07300 myo-inositol ABC transport, substrate-binding component curated:reanno::Phaeo:GFF715 PGA1_c07310 myo-inositol ABC transporter, permease component curated:reanno::Phaeo:GFF716 PGA1_c07320 myo-inositol ABC transporter, ATPase component curated:reanno::Phaeo:GFF717 # Transporters were identified using: # query: transporter:myo-inositol:myoinositol:m-inositol:inositol myo-inositol-transport: PGA1_c07300 PGA1_c07310 PGA1_c07320 iatP myo-inositol ABC transporter, permease component IatP curated:TCDB::B8H230 iatA myo-inositol ABC transporter, ATPase component IatA curated:TCDB::B8H229 ibpA myo-inositol ABC transporter, substrate-binding component IbpA curated:TCDB::B8H228 myo-inositol-transport: iatP iatA ibpA # The ortholog in P. fluorescens FW300-N2E3 (AO353_21380, A0A0N9WNI6) # was not reannotated but does have the phenotype PS417_11885 myo-inositol ABC transporter, substrate-binding component curated:reanno::WCS417:GFF2331 uniprot:A0A0N9WNI6 PS417_11890 myo-inositol ABC transporter, ATPase component curated:reanno::WCS417:GFF2332 curated:reanno::pseudo3_N2E3:AO353_21385 PS417_11895 myo-inositol ABC transporter, permease component curated:reanno::WCS417:GFF2333 curated:reanno::pseudo3_N2E3:AO353_21390 myo-inositol-transport: PS417_11885 PS417_11890 PS417_11895 # Homomeric transporters # Distantly related transporters with the same domain content were grouped together into iolT iolT myo-inositol:H+ symporter curated:SwissProt::Q8VZR6 curated:CharProtDB::CH_091483 curated:CharProtDB::CH_091623 curated:CharProtDB::CH_123508 curated:SwissProt::O34718 curated:SwissProt::P30606 curated:SwissProt::P87110 curated:SwissProt::Q10286 curated:TCDB::A8DCT2 curated:TCDB::AIU34725.1 curated:TCDB::Q01440 curated:TCDB::Q8NTX0 curated:TCDB::E1WAV3 curated:TCDB::E1WAV4 curated:TCDB::Q8NL90 curated:CharProtDB::CH_123411 curated:CharProtDB::CH_124311 myo-inositol-transport: iolT SMIT1 myo-inositol:Na+ symporter curated:SwissProt::Q28728 curated:SwissProt::Q8K0E3 curated:SwissProt::Q8WWX8 curated:SwissProt::Q9JKZ2 curated:SwissProt::Q9Z1F2 curated:TCDB::P31637 curated:TCDB::P53794 myo-inositol-transport: SMIT1 HMIT myo-inositol:H+ symporter curated:CharProtDB::CH_091598 curated:SwissProt::Q921A2 curated:SwissProt::Q96QE2 curated:SwissProt::Q9C757 curated:SwissProt::Q9ZQP6 myo-inositol-transport: HMIT iolF myo-inositol:H+ symporter curated:SwissProt::P42417 myo-inositol-transport: iolF import glucosamine.steps:kdgK # 2-keto-3-deoxygluconate kinase import glucose.steps:eda # 2-keto-3-deoxygluconate 6-phosphate aldolase import fructose.steps:tpi # triose-phosphate isomerase # 2-oxidation of myo-inositol is also linked to EC:1.1.5.n1 (quinoprotein inositol dehydrogenase), # but that is not linked to sequence iolG myo-inositol 2-dehydrogenase EC:1.1.1.18 iolE scyllo-inosose 2-dehydratase EC:4.2.1.44 # Erroneous annotations of epi-inositol hydrolases from SEED were "confirmed" by the fitness data and included in # reannotations; these are all ignored. iolD 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase EC:3.7.1.22 ignore_other:epi-inositol hydrolase # The EC number is missing from the reannotations iolB 5-deoxy-D-glucuronate isomerase EC:5.3.1.30 term:5-deoxy-glucuronate isomerase iolC 5-dehydro-2-deoxy-D-gluconate kinase EC:2.7.1.92 # DUF2090 appears to be a substitute for the aldolase. It is distantly related to aldolases # and is found fused to iolC in inositol degradation clusters that lack any apparent iolJ. # Fitness data confirms that these fusion proteins are required for myo-inositol utilization # (but does not prove that the DUF2090 domain is required). # These proteins are included in iolJ via their reannotations. iolJ 5-dehydro-2-deoxyphosphogluconate aldolase EC:4.1.2.29 # Related to methylmalonate-semialdehyde dehydrogenase (1.2.1.27), and many enzymes # may have both activities. # Q9I702 is annotated as doing this but as "putative" and without the EC number mmsA malonate-semialdehyde dehydrogenase EC:1.2.1.18 ignore_other:1.2.1.27 ignore:SwissProt::Q9I702 # Both pathways begin with the 2-dehydrogenase (iolG) forming scyllo-inosose. # In pathway I, inosose dehydratase (iolE) forms 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione, # followed by a ring-cleaving hydrolase to 5-deoxy-D-glucuronate, # isomerization to 5-dehydro-2-deoxy-D-gluconate, phosphorylation, # and cleavage by an aldolase to 3-oxopropionate (malonate semialdehyde) and # glycerone phosphate; the 3-oxopropionate is oxidized to acetyl-CoA while the # glycerone phosphate is converted by triose-phosphate isomerase to glyceraldehyde 3-phosphate. all: myo-inositol-transport iolG iolE iolD iolB iolC iolJ mmsA tpi iolM 2-inosose 4-dehydrogenase curated:metacyc::MONOMER-17949 iolN 2,4-diketo-inositol hydratase curated:SwissProt::Q9WYP4 iolO 5-dehydro-L-gluconate epimerase curated:SwissProt::Q9WYP7 uxaE D-tagaturonate epimerase EC:5.1.2.7 uxuB D-mannonate dehydrogenase EC:1.1.1.57 # Many proteins are annotated in SwissProt as "D-galactonate dehydratase family member" but # have little activity on D-mannonoate; it is probably not the physiological substrate uxuA D-mannonate dehydratase EC:4.2.1.8 ignore:SwissProt::A4WA78 ignore:SwissProt::A5KUH4 ignore:SwissProt::A6AMN2 ignore:SwissProt::A6M2W4 ignore:SwissProt::A6VRA1 ignore:SwissProt::A8RQK7 ignore:SwissProt::B1ELW6 ignore:SwissProt::B3PDB1 ignore:SwissProt::B5GCP6 ignore:SwissProt::B5QBD4 ignore:SwissProt::B5R541 ignore:SwissProt::B5RAG0 ignore:SwissProt::B8HCK2 ignore:SwissProt::C6CBG9 ignore:SwissProt::C6CVY9 ignore:SwissProt::C6D9S0 ignore:SwissProt::C6DI84 ignore:SwissProt::C7PW26 ignore:SwissProt::C8ZZN2 ignore:SwissProt::C9A1P5 ignore:SwissProt::C9CN91 ignore:SwissProt::C9NUM5 ignore:SwissProt::C9Y5D5 ignore:SwissProt::D0KC90 ignore:SwissProt::D0X4R4 ignore:SwissProt::D4GJ14 ignore:SwissProt::D7BPX0 ignore:SwissProt::D8ADB5 ignore:SwissProt::D9UNB2 ignore:SwissProt::E1V4Y0 ignore:SwissProt::Q1QT89 ignore:SwissProt::Q2CIN0 ignore:SwissProt::Q6DAR4 ignore:SwissProt::Q8FHC7 # In pathway II, a dehydrogenase forms 3-dehydro scyllo-inosose (also known as 2,4-diketo-inositol), # a hydratase forms 5-dehydro-L-gluconate, an epimerase forms D-tagaturonate, # another forms to D-fructonate, a reductase forms D-mannonate, a dehydratase forms # 2-keto-3-deoxygluconate, a kinase forms 2-keto-3-deoxy-gluconate 6-phosphate, # and an aldolase forms glyceraldehyde-3-phosphate and pyruvate. all: myo-inositol-transport iolG iolM iolN iolO uxaE uxuB uxuA kdgK eda
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