Definition of propionate catabolism

GapMind for catabolism of small carbon sources

Definition of propionate catabolism

# 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:6.4.1.3

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:6.4.1.3

# 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:6.4.1.3
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit	curated:metacyc::MONOMER-13596	ignore_other:6.4.1.3
# Acidianus brierleyi has a diverged pccA split into two pieces.
propionyl-CoA-carboxylase: pccA1 pccA2 pccB

# Many acetyl-CoA synthetases (EC:6.2.1.1) are also propionyl-CoA synthetases
prpE	propionyl-CoA synthetase	EC:6.2.1.17	ignore_other:6.2.1.1

# P45858 is annotated by SwissProt as 2-methylcitrate synthase, but without this EC number
prpC	2-methylcitrate synthase	EC:2.3.3.5	curated:BRENDA::P45858

prpD	2-methylcitrate dehydratase	EC:4.2.1.79

# (2R,3S)-2-methylcitrate dehydratases are closely related to
# aconitate hydratases (EC:4.2.1.3), which are ignored.
acn	(2R,3S)-2-methylcitrate dehydratase	EC:4.2.1.99	ignore_other:4.2.1.3

# Many 2-methylisocitrate lyases are closely related to isocitrate lyases (EC:4.1.3.1)
prpB	2-methylisocitrate lyase	EC:4.1.3.30	ignore_other:4.1.3.1

# 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:4.2.1.117	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:5.3.3.7	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:5.1.99.1	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:5.4.99.2

mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	curated:BRENDA::A4YEG1	curated:BRENDA::O74009	curated:BRENDA::P11653	ignore_other:5.4.99.2

mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	curated:BRENDA::A4YIE3	curated:BRENDA::O58013	ignore_other:5.4.99.2

# 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:1.3.3.6
hpcD	3-hydroxypropionyl-CoA dehydratase	EC:4.2.1.116
dddA	3-hydroxypropionate dehydrogenase	EC:1.1.1.59

# Ignore similarity to methylmalonate semialdehyde dehydrogenase (EC:1.2.1.27), which often has this activity as well
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	EC:1.2.1.18	ignore_other:1.2.1.27	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:

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
the source code
instructions for running GapMind on your computer

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

GapMind for catabolism of small carbon sources