Definition of 2-deoxy-D-ribose catabolism
As rules and steps, or see full text
Rules
Overview: Deoxyribose utilization in GapMind is based on MetaCyc pathways 2-deoxy-D-ribose degradation I via deoxyribose 5-phosphate aldolase (link) and pathway II via oxidation to 2-deoxy-3-dehydro-D-ribonate (link).
- all:
- deoxyribose-transport, deoK, deoC and acetaldehyde-degradation
- or deoxyribose-dehyd, deoxyribonate-transport and deoxyribonate-degradation
- Comment: The deoxyribose 5-phosphate pathway involves the kinase deoK and the aldolase deoC. The oxidative pathway involves oxidation in the periplasm to deoxyribonate.
- deoxyribonate-degradation: deoxyribonate-dehyd, ketodeoxyribonate-cleavage, garK and acetoacetate-degradation
- Comment: After oxidation of deoxyribonate to 2-deoxy-3-ketoribonate, a cleavage enzyme produces glyceroyl-CoA and acetoacetate; the enzyme for the conversion of glyceroyl-CoA to glycerate is not known; and garK phosphorylates glycerate to 2-phospho-D-glycerate, an intermediate in glycolysis.
- acetoacetate-degradation: acetoacetate-activation and atoB
- Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
- acetoacetate-activation:
- atoA and atoD
- or aacS
- Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
- deoxyribose-dehyd: drdehyd-alpha, drdehyd-beta and drdehyd-cytc
- acetaldehyde-degradation:
- ald-dh-CoA
- or adh and acs
- or adh, ackA and pta
- Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
- deoxyribose-transport: deoP
Steps
deoP: deoxyribose transporter
- Curated sequence Q8XEV7: 2-Deoxy-D-ribose porter, DeoP
- Comment: Salmonella deoP (Q8XEV7) is near deoK and can enhance growth of E. coli on deoxyribose, even though it is not essential for deoxyribose utilization in Salmonella, see PMC94358.
- Total: 1 characterized proteins
deoK: deoxyribokinase
deoC: deoxyribose-5-phosphate aldolase
ald-dh-CoA: acetaldehyde dehydrogenase, acylating
- Curated proteins or TIGRFams with EC 1.2.1.10
- Ignore hits to items matching 1.1.1.1 when looking for 'other' hits
- Ignore hits to items matching 1.1.1.71 when looking for 'other' hits
- Ignore hits to items matching 1.2.1.57 when looking for 'other' hits
- Ignore hits to Q2XQZ7 when looking for 'other' hits (4-hydroxy-2-oxovalerate aldolase (EC 4.1.3.39))
- Comment: Many enzymes are multifunctional alcohol/acetaldehyde dehydrogenases, and many close homologs have just one annotation. EC 1.2.1.57 is acylating butanal dehydrogenase, which may also act on acetaldehyde. Q2XQZ7 is probably misannotated.
- Total: 2 HMMs and 20 characterized proteins
adh: acetaldehyde dehydrogenase (not acylating)
acs: acetyl-CoA synthetase, AMP-forming
ackA: acetate kinase
pta: phosphate acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.8
- Ignore hits to P32796 when looking for 'other' hits (carnitine O-acetyltransferase (EC 2.3.1.7); phosphate acetyltransferase (EC 2.3.1.8). Carnitine O-acetyltransferase, mitochondrial; Carnitine acetylase; EC 2.3.1.7)
- Comment: BRENDA misannotates yeast's carnitine acetyltransferase with EC 2.3.1.8
- Total: 1 HMMs and 18 characterized proteins
drdehyd-alpha: 2-deoxy-D-ribose dehydrogenase, alpha subunit
- Curated proteins matching deoxy%ribose dehydrogenase%alpha
- Ignore hits to items matching vanillin dehydrogenase when looking for 'other' hits
- Comment: This three-component periplasmic (probably) dehydrogenase seems to be non-specific, but it is the only known way to convert deoxyribose to deoxyribonate. (Oxidative damage of DNA and archaeal glycolysis may also be sources of deoxyribonate.) It probably forms 1,5-lactone, but since that is uncertain, the lactonase is not included in this pathway definition
- Total: 1 characterized proteins
drdehyd-beta: 2-deoxy-D-ribose dehydrogenase, beta subunit
drdehyd-cytc: 2-deoxyribose-D dehydrogenase, cytochrome c component
atoA: acetoacetyl-CoA transferase, A subunit
- Curated sequence ATOD-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &alpha. ; acetyl-CoA:acetoacetyl-CoA transferase subunit α
- Curated sequence HP0691-MONOMER: Succinyl-CoA:3-ketoacid coenzyme A transferase subunit A; Succinyl-CoA:3-oxoacid CoA-transferase; OXCT A; EC 2.8.3.5. succinyl-CoA:acetoacetate CoA-transferase subunit A (EC 2.8.3.5)
- Curated sequence GFF1045: acetyl-CoA:acetoacetate CoA transferase, A subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2111: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit A
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
atoD: acetoacetyl-CoA transferase, B subunit
- Curated sequence ATOA-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &beta. ; acetyl-CoA:acetoacetyl-CoA transferase subunit β
- Curated sequence HP0692-MONOMER: succinyl-CoA:acetoacetate CoA-transferase subunit B (EC 2.8.3.5)
- Curated sequence GFF1044: acetyl-CoA:acetoacetate CoA transferase, B subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2112: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit B
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
aacS: acetoacetyl-CoA synthetase
atoB: acetyl-CoA C-acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.9
- Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
- Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
- Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
- Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
- Total: 36 characterized proteins
deoxyribonate-dehyd: 2-deoxy-D-ribonate 3-dehydrogenase
ketodeoxyribonate-cleavage: 2-deoxy-3-keto-D-ribonate cleavage enzyme
garK: glycerate 2-kinase
- Curated proteins or TIGRFams with EC 2.7.1.165
- Curated sequence GFF1145: D-glycerate 2-kinase (EC 2.7.1.-)
- Comment: GarK produces 2-phospho-D-glycerate, an intermediate in glycolysis. psRCH2:GFF1145 is believed to do this reaction but was not annotated with this EC number.
- Total: 11 characterized proteins
deoxyribonate-transport: 2-deoxy-D-ribonate transporter
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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