GapMind for catabolism of small carbon sources


Definition of propionate catabolism

As text, or see rules and steps

# Propionate degradation in GapMind is based on
# MetaCyc pathways for the 2-methylcitrate cycle (metacyc:PWY0-42, metacyc:PWY-5747)
# and for propanoyl-CoA degradation (metacyc:PROPIONMET-PWY, metacyc:PWY-7574).

putP	propionate transporter; proline:Na+ symporter	curated:SwissProt::P07117

# Transporters were identified using:
# query: transporter:propionate:propanoate
propionate-transport: putP

SLC5A8	sodium-coupled monocarboxylate transporter	curated:SwissProt::Q8N695
propionate-transport: SLC5A8

# 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.
lctP	propionate permease	uniprot:A0KZB2	uniprot:Q8EIL2
propionate-transport: lctP

mctC	propionate:H+ symporter	curated:SwissProt::Q8NS49
propionate-transport: mctC

mctP	propionate permease	curated:TCDB::Q8VM88	curated:SwissProt::Q1M7A2
propionate-transport: mctP

# Pdr12p is an exporter, ignored
# Also ignore Best1, a Ca2+ activated anion channel

pccA	propionyl-CoA carboxylase, alpha subunit	curated:BRENDA::P05165	curated:BRENDA::Q19842	curated:SwissProt::I3R7G3	curated:SwissProt::P0DTA4	curated:SwissProt::Q5LUF3	curated:SwissProt::Q91ZA3	curated:metacyc::MONOMER-13589	curated:metacyc::MONOMER-8606	curated:reanno::Dino:3607308	curated:reanno::PS:Dsui_0516	ignore_other:

pccB	propionyl-CoA carboxylase, beta subunit	curated:BRENDA::P05166	curated:BRENDA::Q20676	curated:BRENDA::Q9X4K7	curated:SwissProt::I3R7F1	curated:SwissProt::P53003	curated:SwissProt::P79384	curated:SwissProt::Q168G2	curated:SwissProt::Q3J4E3	curated:SwissProt::Q99MN9	curated:metacyc::MONOMER-13598	curated:metacyc::MONOMER-16260	curated:metacyc::MONOMER-17283	curated:metacyc::MONOMER-17284	curated:metacyc::MONOMER-8607	curated:reanno::Dino:3607303	curated:reanno::PS:Dsui_0517	ignore_other:

# 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.
propionyl-CoA-carboxylase: pccA pccB

pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	curated:metacyc::MONOMER-13597	ignore_other:
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	curated:metacyc::MONOMER-13596	ignore_other:
# Acidianus brierleyi has a diverged pccA split into two pieces.
propionyl-CoA-carboxylase: pccA1 pccA2 pccB

# Many acetyl-CoA synthetases (EC: are also propionyl-CoA synthetases
prpE	propionyl-CoA synthetase	EC:	ignore_other:

# P45858 is annotated by SwissProt as 2-methylcitrate synthase, but without this EC number
prpC	2-methylcitrate synthase	EC:	curated:BRENDA::P45858

prpD	2-methylcitrate dehydratase	EC:

# (2R,3S)-2-methylcitrate dehydratases are closely related to
# aconitate hydratases (EC:, which are ignored.
acn	(2R,3S)-2-methylcitrate dehydratase	EC:	ignore_other:

# Many 2-methylisocitrate lyases are closely related to isocitrate lyases (EC:
prpB	2-methylisocitrate lyase	EC:	ignore_other:

# 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
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	EC:	ignore:SwissProt::Q937N8

# 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.
prpF	methylaconitate isomerase	EC:	curated:SwissProt::Q937N7	ignore:SwissProt::A0A0A1H8I4

# 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).
epi	methylmalonyl-CoA epimerase	EC:	ignore:reanno::Dino:3607309

mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	curated:SwissProt::O86028	curated:BRENDA::P22033	curated:BRENDA::Q23381	curated:BRENDA::Q84FZ1	curated:BRENDA::Q8MI68	curated:SwissProt::P27253	curated:SwissProt::Q3J4D7	curated:metacyc::MONOMER-18293	curated:reanno::PS:Dsui_0519	curated:BRENDA::Q8F222	curated:BRENDA::Q8Y2U5	ignore_other:

mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	curated:BRENDA::A4YEG1	curated:BRENDA::O74009	curated:BRENDA::P11653	ignore_other:

mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	curated:BRENDA::A4YIE3	curated:BRENDA::O58013	ignore_other:

# 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., uniprot:Q8F222, uniprot:Q8Y2U5).
methylmalonyl-CoA-mutase: mcmA
methylmalonyl-CoA-mutase: mcm-large mcm-small

pco	propanyl-CoA oxidase	EC:
hpcD	3-hydroxypropionyl-CoA dehydratase	EC:
dddA	3-hydroxypropionate dehydrogenase	EC:

# Ignore similarity to methylmalonate semialdehyde dehydrogenase (EC:, which often has this activity as well
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	EC:	ignore_other:	ignore:SwissProt::Q9I702

# 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.)
propionyl-CoA-degradation: prpC prpD acn prpB

# 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.
propionyl-CoA-degradation: prpC acnD prpF acn prpB

# 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.)
propionyl-CoA-degradation: propionyl-CoA-carboxylase epi methylmalonyl-CoA-mutase

# 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.
propionyl-CoA-degradation: pco hpcD dddA iolA

# In all of the pathways, propionate is first activated to propionyl-CoA by prpE
propionate-degradation: prpE propionyl-CoA-degradation

all: propionate-transport propionate-degradation



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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:

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:

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