Definition of propionate catabolism

As rules and steps, or see full text

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

Steps

putP: propionate transporter; proline:Na+ symporter

• Curated sequence P07117: Sodium/proline symporter; Proline permease; Propionate transporter. Proline:Na+ symporter, PutP. proline:Na⁺ symporter. proline:Na⁺ symporter
• Total: 1 characterized proteins

SLC5A8: sodium-coupled monocarboxylate transporter

• Curated sequence Q8N695: Sodium-coupled monocarboxylate transporter 1; Apical iodide transporter; Electrogenic sodium monocarboxylate cotransporter; Sodium iodide-related cotransporter; Solute carrier family 5 member 8. Na+-dependent short chain fatty acid transporter SLC5A8 (tumor suppressor gene product, down-regulated in colon cancer) (substrates: lactate, pyruvate, acetate, propionate, butyrate (Km ≈1 mM)) [propionate:Na+ = 1:3] (Miyauchi et al., 2004). Pyroglutamate (5-oxoproline) is also transported in a Na+- coupled mechanism (Miyauchi et al., 2010). SMCT1 and SMCT2 may transport monocarboxylate drugs (e.g. nicotinate and its derivatives) across the intestinal brush boarder membrane
• Total: 1 characterized proteins

lctP: propionate permease

• UniProt sequence A0KZB2: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
• UniProt sequence Q8EIL2: RecName: Full=L-lactate permease {ECO:0000256|RuleBase:RU365092};
• Comment: Shewana3_2904 (A0KZB2) from Shewanella sp. ANA-3 is important for propionate utilization; it is also a lactate permease. Similarly, the distantly related SO0827 from Shewanella oneidensis (Q8EIL2) is important for propionate utilization.
• Total: 2 characterized proteins

mctC: propionate:H+ symporter

• Curated sequence Q8NS49: Monocarboxylic acid transporter. Pyruvate/acetate/propionate: H+ symporter, MctC (DhlC; cg0953)
• Total: 1 characterized proteins

mctP: propionate permease

• Curated sequence Q8VM88: The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine)
• Curated sequence Q1M7A2: Monocarboxylate transport permease protein
• Total: 2 characterized proteins

pccA: propionyl-CoA carboxylase, alpha subunit

• Curated sequence P05165: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3. propionyl-CoA carboxylase α chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q19842: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence I3R7G3: Propionyl-CoA carboxylase, biotin carboxylase and biotin-carboxyl carrier subunit; PCC; EC 6.4.1.3; EC 6.3.4.14. propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Curated sequence P0DTA4: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence Q5LUF3: Propionyl-CoA carboxylase alpha chain; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence Q91ZA3: Propionyl-CoA carboxylase alpha chain, mitochondrial; PCCase subunit alpha; Propanoyl-CoA:carbon dioxide ligase subunit alpha; EC 6.4.1.3
• Curated sequence MONOMER-13589: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8606: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence 3607308: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Curated sequence Dsui_0516: Propionyl-CoA carboxylase biotin-containing subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 10 characterized proteins

pccB: propionyl-CoA carboxylase, beta subunit

• Curated sequence P05166: propionyl-CoA carboxylase (subunit 2/2) (EC 6.4.1.3). Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase β chain, mitochondrial (EC 6.4.1.3)
• Curated sequence Q20676: propionyl-CoA carboxylase (subunit 1/2) (EC 6.4.1.3)
• Curated sequence Q9X4K7: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence I3R7F1: Propionyl-CoA carboxylase, carboxyltransferase subunit; PCC; EC 6.4.1.3. propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence P53003: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3
• Curated sequence P79384: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3
• Curated sequence Q168G2: Propionyl-CoA carboxylase beta chain; EC 6.4.1.3
• Curated sequence Q3J4E3: Propionyl-CoA carboxylase beta chain; PCCase; Propanoyl-CoA:carbon dioxide ligase; EC 6.4.1.3. propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence Q99MN9: Propionyl-CoA carboxylase beta chain, mitochondrial; PCCase subunit beta; Propanoyl-CoA:carbon dioxide ligase subunit beta; EC 6.4.1.3. propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-13598: acyl CoA carboxylase carboxyltransferase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.3)
• Curated sequence MONOMER-16260: propionyl-CoA carboxylase (EC 6.4.1.3)
• Curated sequence MONOMER-17283: propionyl-CoA carboxylase α subunit (EC 6.4.1.3)
• Curated sequence MONOMER-17284: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence MONOMER-8607: propionyl-CoA carboxylase β subunit (EC 6.4.1.3)
• Curated sequence 3607303: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Curated sequence Dsui_0517: Propionyl-CoA carboxylase carboxyl transferase subunit (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 16 characterized proteins

pccA1: propionyl-CoA carboxylase, biotin carboxyl carrier subunit

• Curated sequence MONOMER-13597: acyl CoA carboxylase biotin carboxylase subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). biotin carboxylase (EC 6.3.4.14); acetyl-CoA carboxylase (subunit 2/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 1/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

pccA2: propionyl-CoA carboxylase, biotin carboxylase subunit

• Curated sequence MONOMER-13596: acyl CoA carboxylase biotin carboxyl carrier protein subunit (EC 2.1.3.15; EC 6.4.1.3; EC 6.3.4.14). acetyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.2); propionyl-CoA carboxylase (subunit 3/3) (EC 6.4.1.3)
• Ignore hits to items matching 6.4.1.3 when looking for 'other' hits
• Total: 1 characterized proteins

prpE: propionyl-CoA synthetase

• Curated proteins or TIGRFams with EC 6.2.1.17
• Ignore hits to items matching 6.2.1.1 when looking for 'other' hits
• Comment: Many acetyl-CoA synthetases (EC 6.2.1.1) are also propionyl-CoA synthetases
• Total: 1 HMMs and 15 characterized proteins

prpC: 2-methylcitrate synthase

• Curated proteins or TIGRFams with EC 2.3.3.5
• Curated sequence P45858: citrate synthase (unknown stereospecificity) (EC 2.3.3.16). Citrate/2-methylcitrate synthase; 2-methylcitrate synthase; 2-MCS; MCS; Citrate synthase; EC 2.3.3.-; EC 2.3.3.16
• Comment: P45858 is annotated by SwissProt as 2-methylcitrate synthase, but without this EC number
• Total: 19 characterized proteins

prpD: 2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.79
• Total: 1 HMMs and 11 characterized proteins

acn: (2R,3S)-2-methylcitrate dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.99
• Ignore hits to items matching 4.2.1.3 when looking for 'other' hits
• Comment: (2R,3S)-2-methylcitrate dehydratases are closely related to aconitate hydratases (EC 4.2.1.3), which are ignored.
• Total: 1 HMMs and 10 characterized proteins

prpB: 2-methylisocitrate lyase

• Curated proteins or TIGRFams with EC 4.1.3.30
• Ignore hits to items matching 4.1.3.1 when looking for 'other' hits
• Comment: Many 2-methylisocitrate lyases are closely related to isocitrate lyases (EC 4.1.3.1)
• Total: 1 HMMs and 26 characterized proteins

acnD: 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)

• Curated proteins or TIGRFams with EC 4.2.1.117
• Ignore hits to Q937N8 when looking for 'other' hits (Aconitate hydratase A; Aconitase; (2R,3S)-2-methylisocitrate dehydratase; (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate dehydratase; Iron-responsive protein-like; IRP-like; Probable 2-methyl-cis-aconitate hydratase; RNA-binding protein; EC 4.2.1.3; EC 4.2.1.99)
• Comment: acnM from Ralstonia eutropha (Q937N8) is proposed to have this activity as well (PMID:11495997), but is annotated in SwissProt as aconitase or (2R,3S)-2-methylisocitrate dehydratase instead
• Total: 1 characterized proteins

prpF: methylaconitate isomerase

• Curated proteins or TIGRFams with EC 5.3.3.7
• Curated sequence Q937N7: 2-methyl-aconitate isomerase; Cis-trans isomerase; EC 5.3.3.-
• Ignore hits to A0A0A1H8I4 when looking for 'other' hits (Aconitate isomerase; AI; EC 5.3.3.7. aconitate DELTA-isomerase (EC 5.3.3.7))
• Comment: SwissProt annotates Q937N7 with this activity, but with a vague EC number. The periplasmic substrate-binding protein A0A0A1H8I4 has aconitate isomerase activity but has a high Km (PMID:26293748), and its periplasmic location would prevent it from participating in the methylcitrate cycle, so it is ignored.
• Total: 3 characterized proteins

epi: methylmalonyl-CoA epimerase

• Curated proteins or TIGRFams with EC 5.1.99.1
• Ignore hits to 3607309 when looking for 'other' hits (Methylmalonyl-CoA epimerase (EC 5.1.99.1))
• Comment: In the fitness browser reannotations, Dshi_0724 from Dinoroseobacter shibae (Dino:3607309) was annotated as the epimerase because it was annotated as such by SEED and it has a specific phenotype on propionate, which seemed to confirm its annotation. But Dshi_0724 belongs to the uncharacterized family DUF4174 / PF13778 and has a signal peptide. Also, D. shibae contains another, apparently essential, epi (Dshi_2630).
• Total: 1 HMMs and 9 characterized proteins

mcmA: methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components

• Curated sequence O86028: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2
• Curated sequence P22033: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase, mitochondrial; MCM; Methylmalonyl-CoA isomerase; EC 5.4.99.2. Methylmalonyl-CoA mutase, mitochondrial (EC 5.4.99.2)
• Curated sequence Q23381: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q84FZ1: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8MI68: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence P27253: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2). methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q3J4D7: Methylmalonyl-CoA mutase; MCM; EC 5.4.99.2. methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence MONOMER-18293: methylmalonyl-CoA mutase subunit (EC 5.4.99.2)
• Curated sequence Dsui_0519: Methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8F222: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Curated sequence Q8Y2U5: methylmalonyl-CoA mutase (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 11 characterized proteins

mcm-large: methylmalonyl-CoA mutase, large (catalytic) subunit

• Curated sequence A4YEG1: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence O74009: methylmalonyl-CoA mutase (subunit 2/2) (EC 5.4.99.2)
• Curated sequence P11653: methylmalonyl-CoA mutase (EC 5.4.99.2). Methylmalonyl-CoA mutase large subunit; MCM-alpha; EC 5.4.99.2. methylmalonyl-CoA mutase large subunit (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 3 characterized proteins

mcm-small: methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit

• Curated sequence A4YIE3: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Curated sequence O58013: methylmalonyl-CoA mutase (subunit 1/2) (EC 5.4.99.2)
• Ignore hits to items matching 5.4.99.2 when looking for 'other' hits
• Total: 2 characterized proteins

pco: propanyl-CoA oxidase

• Curated proteins or TIGRFams with EC 1.3.3.6
• Total: 27 characterized proteins

hpcD: 3-hydroxypropionyl-CoA dehydratase

• Curated proteins or TIGRFams with EC 4.2.1.116
• Total: 3 characterized proteins

dddA: 3-hydroxypropionate dehydrogenase

• Curated proteins or TIGRFams with EC 1.1.1.59
• Total: 2 characterized proteins

iolA: malonate semialdehyde dehydrogenase (CoA-acylating)

• Curated proteins or TIGRFams with EC 1.2.1.18
• Ignore hits to items matching 1.2.1.27 when looking for 'other' hits
• Ignore hits to Q9I702 when looking for 'other' hits (Putative 3-oxopropanoate dehydrogenase; EC 1.2.1.-)
• Comment: Ignore similarity to methylmalonate semialdehyde dehydrogenase (EC 1.2.1.27), which often has this activity as well
• Total: 11 characterized proteins