propionate catabolism in Thermodesulforhabdus norvegica DSM 9990

GapMind for catabolism of small carbon sources

propionate catabolism in Thermodesulforhabdus norvegica DSM 9990

Best path

putP, prpE, pccA, pccB, epi, mcm-large, mcm-small

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 (14 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
putP	propionate transporter; proline:Na+ symporter
prpE	propionyl-CoA synthetase	BM091_RS11480	BM091_RS04165
pccA	propionyl-CoA carboxylase, alpha subunit	BM091_RS08670
pccB	propionyl-CoA carboxylase, beta subunit	BM091_RS01080	BM091_RS08950
epi	methylmalonyl-CoA epimerase	BM091_RS09535
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BM091_RS09525	BM091_RS05135
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BM091_RS09530	BM091_RS05130
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BM091_RS00015	BM091_RS09505
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BM091_RS00015	BM091_RS09505
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	BM091_RS07560	BM091_RS06670
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BM091_RS10135
lctP	propionate permease
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BM091_RS09525	BM091_RS05135
mctC	propionate:H+ symporter
mctP	propionate permease
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BM091_RS08670
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	BM091_RS00780	BM091_RS13360
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase	BM091_RS00050
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.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

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