propionate catabolism in Desulfotomaculum hydrothermale Lam5
Best path
lctP, prpE, pccA, pccB, epi, mcmA
Rules
Overview: Propionate degradation in GapMind is based on MetaCyc pathways for the 2-methylcitrate cycle (link, link) and for propanoyl-CoA degradation (link, link).
- all: propionate-transport and propionate-degradation
- propionate-degradation: prpE and propionyl-CoA-degradation
- Comment: In all of the pathways, propionate is first activated to propionyl-CoA by prpE
- propionyl-CoA-degradation:
- prpC, prpD, acn and prpB
- or prpC, acnD, prpF, acn and prpB
- or propionyl-CoA-carboxylase, epi and methylmalonyl-CoA-mutase
- or pco, hpcD, dddA and iolA
- Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: propionyl-CoA is oxidized to acrylyl-CoA by pco, hydrated to 3-hydroxypropionyl-CoA, hydrolzed to 3-hydroxypropionate, oxidized to 3-oxopropionate (malonate semialdehyde), and oxidized to acetyl-CoA and CO2.
- methylmalonyl-CoA-mutase:
- mcmA
- or mcm-large and mcm-small
- Comment: methylmalonyl-CoA mutase has a catalytic domain and a B12-binding domain. These are usually found in the same protein, which we call mcmA. In Metallosphaera and Pyrococcus, the B12-binding domain is a separate subunit. In Propionibacterium and Methylorubrum, there is an additional subunit with a catalytic domain only; this may have a protective role (PMID:14734568) and is not described here. There's also a mcm-interacting GTPase (known as MeaB or YgfD) that loads B12 onto mcm and protects it from inactivation (see PMC4631608); this is not described here. Some fused mcm proteins include a MeaB domain as well (i.e., Q8F222, Q8Y2U5).
- propionyl-CoA-carboxylase:
- pccA and pccB
- or pccA1, pccA2 and pccB
- Comment: propionyl-CoA carboxylase is a heteromer, usually with alpha and beta subunits pccAB. Haloferax mediterranei has a third subunit as well (pccX), which is not described here. Acidianus brierleyi has a diverged pccA split into two pieces.
- propionate-transport:
- putP
- or SLC5A8
- or lctP
- or mctC
- or mctP
- Comment: Transporters were identified using: query: transporter:propionate:propanoate
24 steps (6 with candidates)
Or see definitions of steps
| Step | Description | Best candidate | 2nd candidate |
|---|
| lctP | propionate permease | DESHY_RS00630 | DESHY_RS00625 |
| prpE | propionyl-CoA synthetase | DESHY_RS06080 | DESHY_RS12640 |
| pccA | propionyl-CoA carboxylase, alpha subunit | DESHY_RS10455 | |
| pccB | propionyl-CoA carboxylase, beta subunit | | |
| epi | methylmalonyl-CoA epimerase | | |
| mcmA | methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components | | |
| Alternative steps: |
| acn | (2R,3S)-2-methylcitrate dehydratase | | |
| acnD | 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming) | | |
| dddA | 3-hydroxypropionate dehydrogenase | | |
| hpcD | 3-hydroxypropionyl-CoA dehydratase | | |
| iolA | malonate semialdehyde dehydrogenase (CoA-acylating) | DESHY_RS11965 | |
| mcm-large | methylmalonyl-CoA mutase, large (catalytic) subunit | | |
| mcm-small | methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit | | |
| mctC | propionate:H+ symporter | | |
| mctP | propionate permease | | |
| pccA1 | propionyl-CoA carboxylase, biotin carboxyl carrier subunit | DESHY_RS10455 | |
| pccA2 | propionyl-CoA carboxylase, biotin carboxylase subunit | | |
| pco | propanyl-CoA oxidase | DESHY_RS06335 | |
| prpB | 2-methylisocitrate lyase | | |
| prpC | 2-methylcitrate synthase | | |
| prpD | 2-methylcitrate dehydratase | | |
| prpF | methylaconitate isomerase | | |
| putP | propionate transporter; proline:Na+ symporter | | |
| SLC5A8 | sodium-coupled monocarboxylate transporter | | |
Confidence: high confidence medium confidence low confidence
transporter – transporters and PTS systems are shaded because predicting their specificity is particularly challenging.
This GapMind analysis is from Sep 24 2021. The underlying query database was built on Sep 17 2021.
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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:
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