L-proline catabolism in Methylobacterium sp. 4-46

GapMind for catabolism of small carbon sources

L-proline catabolism in Methylobacterium sp. 4-46

Best path

AZOBR_RS08235, AZOBR_RS08240, AZOBR_RS08245, AZOBR_RS08250, AZOBR_RS08260, put1, putA

Rules

Overview: Proline degradation in GapMind is based on MetaCyc pathway I via glutamate semialdehyde dehydrogenase (link) and pathway II via 5-aminopentanoate (link). (MetaCyc describes 5-aminopentanoate, also known as 5-aminovalerate, as a fermentative end product, but it is further degraded

all: proline-transport and proline-degradation
proline-degradation:

put1 and putA
or prdF, D-proline-reductase and 5-aminovalerate-degradation
Comment: In pathway I, proline dehydrogenase (put1) forms (S)-1-pyrroline-5-carboxylate, which spontaneously hydrates to L-glutamate 5-semialdehyde, and a dehydrogenase (putA) to glutamate. Glutamate can be transaminated to 2-oxoglutarate, which is an intermediate in central metabolism (not represented). In pathway II, proline racemase (prdF) forms D-proline, and a reductase forms 5-aminovalerate.

5-aminovalerate-degradation: davT, davD and glutarate-degradation

Comment: 5-aminovalerate is an intermediate in L-lysine degradation (link, link). It is transaminated to glutarate semialdehyde and oxidized to glutarate. (A fermentative pathway via 5-hydroxyvalerate has also been reported, but does not seem to be fully linked to sequence; see pathway 5 of PMID:11759672.)

glutarate-degradation:

glaH and lhgD
or gcdG and glutaryl-CoA-degradation
Comment: Glutarate is an intermediate in L-lysine degradation. As part of MetaCyc pathway L-lysine degradation I (link), gluratate is hydroxylated to L-2-hydroxyglutarate (also known as (S)-2-hydroxyglutarate) by a 2-oxoglutarate-dependent oxidase. This reaction releases succinate (a TCA cycle intermediate) and CO2. A dehydrogenase then oxidizes to L-2-hydroxyglutarate to regenerate 2-oxoglutarate. Alternatively, as part of pathway IV (link), glutarate can be activated to glutaryl-CoA by a CoA-transferase. Glutaryl-CoA degradation (link) involves glutaryl-CoA dehydrogenase (decarboxylating) to crotonyl-CoA (trans-but-2-enoyl-CoA), hydration to (S)-hydroxybutanoyl-CoA, oxidization to acetoacetyl-CoA, and cleavage by a C-acetyltransferase to two acetyl-CoA.

glutaryl-CoA-degradation: gcdH, ech, fadB and atoB

Comment: In MetaCyc pathway glutaryl-CoA degradation (link), glutaryl-CoA is oxidized to (E)-glutaconyl-CoA and oxidatively decarboxylated to crotonyl-CoA (both by the same enzyme), hydrated to 3-hydroxybutanoyl-CoA, oxidized to acetoacetyl-CoA, and cleaved to two acetyl-CoA.

D-proline-reductase: prdA, prdB and prdC

Comment: D-proline reductase includes components PrdA and PrdB and electron transfer protein PrdC

proline-transport:

proV, proW and proX
or opuBA and opuBB
or natA, natB, natC, natD and natE
or hutV, hutW and hutX
or AZOBR_RS08235, AZOBR_RS08240, AZOBR_RS08245, AZOBR_RS08250 and AZOBR_RS08260
or HSERO_RS00870, HSERO_RS00885, HSERO_RS00890, HSERO_RS00895 and HSERO_RS00900
or aapJ, aapQ, aapM and aapP
or proY
or putP
or PROT1
or SLC6A7
or proP
or ectP
or betS
or BAC2
or AAT20.2
or CCNA_00435
or N515DRAFT_2924
Comment: Transporters were identified using query: transporter:proline:L-proline

53 steps (38 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
AZOBR_RS08235	proline ABC transporter, permease component 1	M446_RS26265	M446_RS27480
AZOBR_RS08240	proline ABC transporter, permease component 2	M446_RS26260	M446_RS31395
AZOBR_RS08245	proline ABC transporter, ATPase component 1	M446_RS26255	M446_RS10785
AZOBR_RS08250	proline ABC transporter, ATPase component 2	M446_RS26245	M446_RS09120
AZOBR_RS08260	proline ABC transporter, substrate-binding component	M446_RS22575	M446_RS01575
put1	proline dehydrogenase	M446_RS10455	M446_RS18520
putA	L-glutamate 5-semialdeyde dehydrogenase	M446_RS10455	M446_RS18485
Alternative steps:
aapJ	ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), substrate-binding component AapJ	M446_RS28350
aapM	ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 2 (AapM)	M446_RS28360	M446_RS21780
aapP	ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), ATPase component AapP	M446_RS28365	M446_RS08220
aapQ	ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 1 (AapQ)	M446_RS28355	M446_RS21775
AAT20.2	proline transporter
atoB	acetyl-CoA C-acetyltransferase	M446_RS25460	M446_RS05920
BAC2	basic amino acid carrier BAC2
betS	proline transporter BetS
CCNA_00435	proline transporter	M446_RS09515
davD	glutarate semialdehyde dehydrogenase	M446_RS03820	M446_RS05595
davT	5-aminovalerate aminotransferase	M446_RS31620	M446_RS15500
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	M446_RS22080	M446_RS01130
ectP	proline transporter EctP
fadB	(S)-3-hydroxybutanoyl-CoA dehydrogenase	M446_RS01130	M446_RS15720
gcdG	succinyl-CoA:glutarate CoA-transferase	M446_RS07730	M446_RS16335
gcdH	glutaryl-CoA dehydrogenase	M446_RS07765	M446_RS11035
glaH	glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
HSERO_RS00870	proline ABC transporter, substrate-binding component	M446_RS26235	M446_RS22575
HSERO_RS00885	proline ABC transporter, permease component 1	M446_RS26265	M446_RS31390
HSERO_RS00890	proline ABC transporter, permease component 2	M446_RS26260	M446_RS08490
HSERO_RS00895	proline ABC transporter, ATPase component 1	M446_RS10785	M446_RS08490
HSERO_RS00900	proline ABC transporter, ATPase component 2	M446_RS27465	M446_RS26245
hutV	proline ABC transporter, ATPase component HutV	M446_RS02335	M446_RS30880
hutW	proline ABC transporter, permease component HutW	M446_RS00085
hutX	proline ABC transporter, substrate-binding component HutX
lhgD	L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)	M446_RS01070
N515DRAFT_2924	proline transporter	M446_RS09515
natA	proline ABC transporter, ATPase component 1 (NatA)	M446_RS18410	M446_RS10785
natB	proline ABC transporter, substrate-binding component NatB	M446_RS18395
natC	proline ABC transporter, permease component 1 (NatC)	M446_RS18405
natD	proline ABC transporter, permease component 2 (NatD)	M446_RS18400	M446_RS27480
natE	proline ABC transporter, ATPase component 2 (NatE)	M446_RS35545	M446_RS08485
opuBA	proline ABC transporter, ATPase component OpuBA/BusAA	M446_RS02335	M446_RS07725
opuBB	proline ABC transporter, fused permease and substrate-binding components OpuBB/BusAB
prdA	D-proline reductase, prdA component
prdB	D-proline reductase, prdB component
prdC	D-proline reductase, electron transfer component PrdC
prdF	proline racemase	M446_RS18385
proP	proline:H+ symporter ProP	M446_RS16980	M446_RS23220
PROT1	proline transporter
proV	proline ABC transporter, ATPase component ProV	M446_RS30880	M446_RS02335
proW	proline ABC transporter, permease component ProW	M446_RS21510
proX	proline ABC transporter, substrate-binding component ProX
proY	proline:H+ symporter
putP	proline:Na+ symporter
SLC6A7	proline:Na+ symporter

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