propionate catabolism in Halobacillus alkaliphilus FP5

GapMind for catabolism of small carbon sources

propionate catabolism in Halobacillus alkaliphilus FP5

Best path

lctP, 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 (21 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
lctP	propionate permease	BMZ06_RS19705	BMZ06_RS01570
prpE	propionyl-CoA synthetase	BMZ06_RS09710	BMZ06_RS02730
pccA	propionyl-CoA carboxylase, alpha subunit	BMZ06_RS00985	BMZ06_RS02705
pccB	propionyl-CoA carboxylase, beta subunit	BMZ06_RS01160	BMZ06_RS02725
epi	methylmalonyl-CoA epimerase	BMZ06_RS01155	BMZ06_RS13600
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	BMZ06_RS01150	BMZ06_RS06725
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BMZ06_RS01155	BMZ06_RS06725
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BMZ06_RS19330
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BMZ06_RS19330
dddA	3-hydroxypropionate dehydrogenase	BMZ06_RS07640	BMZ06_RS18265
hpcD	3-hydroxypropionyl-CoA dehydratase	BMZ06_RS18940	BMZ06_RS02720
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BMZ06_RS10420	BMZ06_RS09860
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BMZ06_RS06725	BMZ06_RS01150
mctC	propionate:H+ symporter	BMZ06_RS11800
mctP	propionate permease
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	BMZ06_RS00985	BMZ06_RS02705
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	BMZ06_RS06705	BMZ06_RS02695
prpB	2-methylisocitrate lyase	BMZ06_RS09405	BMZ06_RS18870
prpC	2-methylcitrate synthase	BMZ06_RS12400
prpD	2-methylcitrate dehydratase	BMZ06_RS18865
prpF	methylaconitate isomerase
putP	propionate transporter; proline:Na+ symporter	BMZ06_RS08330
SLC5A8	sodium-coupled monocarboxylate transporter	BMZ06_RS06145

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