Definition of L-proline catabolism

GapMind for catabolism of small carbon sources

Definition of L-proline catabolism

# Proline degradation in GapMind is based on
# MetaCyc pathway I via glutamate semialdehyde dehydrogenase (metacyc:PROUT-PWY)
# and pathway II via 5-aminopentanoate (metacyc:PWY-8186).
# (MetaCyc describes 5-aminopentanoate, also known as 5-aminovalerate, as a
#  fermentative end product, but it is further degraded 

# ABC transporters:

# E.coli/Salmonella have proVWX (only ProV is curated in S. typhimurium).
# Ignore a similar system in Dickeya dadantii (or Erwinia chrysanthemi) reported to act on glycine betaine only
proV	proline ABC transporter, ATPase component ProV	curated:CharProtDB::CH_001555	curated:SwissProt::P17328	ignore:SwissProt::E0SCY1
proW	proline ABC transporter, permease component ProW	curated:SwissProt::P14176	ignore:SwissProt::E0SCY2
proX	proline ABC transporter, substrate-binding component ProX	curated:CharProtDB::CH_024698	ignore:SwissProt::E0SCY3

# Transporters were identified using query: transporter:proline:L-proline
proline-transport: proV proW proX

# In Listeria monocytogenes and in Lactococcus lactis, the permease is fused to the substrate-binding component.
opuBA	proline ABC transporter, ATPase component OpuBA/BusAA	curated:TCDB::Q93A35	curated:TCDB::Q9RQ06
# Ignore a nearly-identical protein from L. lactis, annotated as a quarternary amine transporter
opuBB	proline ABC transporter, fused permease and substrate-binding components OpuBB/BusAB	curated:TCDB::Q93A34	curated:TCDB::Q9RQ05	ignore:BRENDA::Q7DAU8
proline-transport: opuBA opuBB

# Synechocystis sp. NatABCDE; also a similar system in Anabaena
natA	proline ABC transporter, ATPase component 1 (NatA)	curated:TCDB::Q55164	curated:TCDB::Q7A2H0
natB	proline ABC transporter, substrate-binding component NatB	curated:TCDB::Q55387	curated:TCDB::Q8YVY4
natC	proline ABC transporter, permease component 1 (NatC)	curated:TCDB::P74455	curated:TCDB::Q8YY08
natD	proline ABC transporter, permease component 2 (NatD)	curated:TCDB::P74318	curated:TCDB::Q8YXD0
natE	proline ABC transporter, ATPase component 2 (NatE)	curated:TCDB::P73650	curated:TCDB::Q8YT15
proline-transport: natA natB natC natD natE

# Ensifer meliloti (formerly Rhizobium or Sinorhizobium) hutVWX
hutV	proline ABC transporter, ATPase component HutV	curated:TCDB::Q9KKE1
hutW	proline ABC transporter, permease component HutW	curated:TCDB::Q9KKE2
hutX	proline ABC transporter, substrate-binding component HutX	curated:TCDB::Q9KKE3
proline-transport: hutV hutW hutX

# Azospirillum brasilense -- just one component is in the reannotations, but
# all show up in the fitness data for proline.
AZOBR_RS08235	proline ABC transporter, permease component 1	curated:reanno::azobra:AZOBR_RS08235
AZOBR_RS08240	proline ABC transporter, permease component 2	uniprot:G8ALI9
AZOBR_RS08245	proline ABC transporter, ATPase component 1	uniprot:G8ALJ0
AZOBR_RS08250	proline ABC transporter, ATPase component 2	uniprot:G8ALJ1
AZOBR_RS08260	proline ABC transporter, substrate-binding component	uniprot:G8ALJ3
proline-transport: AZOBR_RS08235 AZOBR_RS08240 AZOBR_RS08245 AZOBR_RS08250 AZOBR_RS08260

# 5-part ABC transporter in Herbaspirillum brasilense, identified using fitness data.
# (This system is distantly related to AZOBR_RS08235:RS08260.)
# A related system from Acidovorax sp. GW101-3H11 is also important for proline utilization:
# Ac3H11_2396 (A0A165KTD4), Ac3H11_1695 (A0A165KC95), Ac3H11_1694 (A0A165KER0),
# Ac3H11_1693 (A0A165KC86), Ac3H11_1692 (A0A165KC78).
HSERO_RS00870	proline ABC transporter, substrate-binding component	uniprot:D8IUY1	uniprot:A0A165KTD4
HSERO_RS00885	proline ABC transporter, permease component 1	uniprot:D8IUY4	uniprot:A0A165KC95
HSERO_RS00890	proline ABC transporter, permease component 2	uniprot:D8IUY5	uniprot:A0A165KER0
HSERO_RS00895	proline ABC transporter, ATPase component 1	uniprot:D8J1T6	uniprot:A0A165KC86
HSERO_RS00900	proline ABC transporter, ATPase component 2	uniprot:D8IUY7	uniprot:A0A165KC78
proline-transport: HSERO_RS00870 HSERO_RS00885 HSERO_RS00890 HSERO_RS00895 HSERO_RS00900

# AapJQMP from Rhizobium leguminosarum is described in glutamate.steps
import glutamate.steps:aapJ aapQ aapM aapP
proline-transport: aapJ aapQ aapM aapP

# Other transporters:

proY	proline:H+ symporter	curated:TCDB::Q2VQZ4	curated:CharProtDB::CH_091285	curated:CharProtDB::CH_122066	curated:SwissProt::P46349	curated:SwissProt::Q9URZ3	curated:TCDB::P0AAE2	curated:TCDB::P37460
proline-transport: proY

putP	proline:Na+ symporter	curated:SwissProt::O06493	curated:SwissProt::P07117	curated:SwissProt::P94392	curated:SwissProt::Q2FWY7	curated:TCDB::O24896	curated:TCDB::Q9I5F5
proline-transport: putP

PROT1	proline transporter	curated:CharProtDB::CH_091590	curated:SwissProt::P92962	curated:SwissProt::Q60DN5	curated:SwissProt::Q9SJP9	curated:TCDB::Q9XE48
proline-transport: PROT1

SLC6A7	proline:Na+ symporter	curated:CharProtDB::CH_091144	curated:SwissProt::Q64093	curated:TCDB::P48065	curated:TCDB::Q99884
proline-transport: SLC6A7

proP	proline:H+ symporter ProP	curated:CharProtDB::CH_024324	curated:SwissProt::Q47421	curated:SwissProt::Q79VC4
proline-transport: proP

ectP	proline transporter EctP	curated:SwissProt::Q79VE0	curated:SwissProt::Q87NZ5	curated:SwissProt::Q87PP5
proline-transport: ectP

betS	proline transporter BetS	curated:SwissProt::G3XCN6
proline-transport: betS

BAC2	basic amino acid carrier BAC2	curated:SwissProt::Q9CA93
proline-transport: BAC2

AAT20.2	proline transporter	curated:TCDB::A4HUI4
proline-transport: AAT20.2

# Identified using fitness data for Caulobacter crescentus
CCNA_00435	proline transporter	uniprot:A0A0H3C3Q5
proline-transport: CCNA_00435

# Identified using fitness data for Dyella japonica
N515DRAFT_2924	proline transporter	uniprot:A0A1I1Y8J0
proline-transport: N515DRAFT_2924

# Ignore SLC7A8, not sure if it has much activity as a proline transporter
# Ignore OdpB, a porin

# formerly EC:1.5.99.8
put1	proline dehydrogenase	EC:1.5.5.2	EC:1.5.99.8
# formerly known as 1-pyrroline-5-carboxylate dehydrogenase (EC:1.5.1.12)
putA	L-glutamate 5-semialdeyde dehydrogenase	EC:1.2.1.88	EC:1.5.1.12

# Q4D480 is misannotated in BRENDA.
prdF	proline racemase	EC:5.1.1.4	ignore:BRENDA::Q4D480

prdA	D-proline reductase, prdA component	curated:CharProtDB::CH_013105	curated:SwissProt::Q9Z4P6	ignore_other:1.21.4.1

prdB	D-proline reductase, prdB component	curated:BRENDA::Q17ZY6	curated:CharProtDB::CH_013103	ignore_other:1.21.4.1

# PrdC is identified as CLOST_2236 (E3PU00) by PMC3091704
prdC	D-proline reductase, electron transfer component PrdC	uniprot:E3PU00

# D-proline reductase includes components PrdA and PrdB and electron transfer protein PrdC
D-proline-reductase: prdA prdB prdC

import leucine.steps:atoB # acetyl-CoA acetyltransferase is part of glutaryl-CoA degradation
import phenylacetate.steps:glutaryl-CoA-degradation # glutaryl-CoA is part of 5-aminovalerate degradation
import lysine.steps:5-aminovalerate-degradation

# 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).
proline-degradation: put1 putA

# In pathway II, proline racemase (prdF) forms D-proline, and
# a reductase forms 5-aminovalerate.
proline-degradation: prdF D-proline-reductase 5-aminovalerate-degradation

all: proline-transport proline-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