GapMind for catabolism of small carbon sources


Definition of D-fructose catabolism

As text, or see rules and steps

# Many bacteria take up fructose by a phosphotransferase (PTS) system
# that forms fructose 1-phosphate; this can be consumed via 1-phosphofructokinase
# and glycolysis (metacyc:PWY0-1314).
# Alternatively, some PTS systems form fructose 6-phosphate, which is
# a central metabolic intermediate.
# Fructose can also be taken up directly and then phosphorylated to
# fructose 6-phosphate, a central metabolic intermediate.
# Another path is known in Aeromonas hydrophila -- phosphofructomutase
# converts fructose 1-phosphate (formed by a PTS system) to fructose
# 6-phosphate (PMID:9579084). This path is not included in GapMind because
# phosphofructomutase has not been linked to sequence.
# Also, in eukaryotes, fructose-1,6-bisphosphate aldolase is reported
# to cleave fructose 1-phosphate to glycerone phosphate and glyceraldehyde
# (metacyc:PWY66-373). This would make 1-phosphofructokinase
# unnececessary. It's not clear that this occurs in prokaryotes, so
# this is not listed.

# Two classes of phosphotransferase systems:
# PTS 4.A.2.* produce fructose 1-phosphate, while other PTS produce fructose 6-phosphate

# FruA/FruB:
#   E. coli: FruA has EII-B'BC
#     FruB includes E-IIA and also an HPr domain
#     Also a paralogous system frvAB, TC 4.A.2.1.25 (P32154,P32155), but it is not actually characterized
#   Deinococcus radiodurans has FruA-like II-BC; the adjacent II-A is a pseudogene, but it still functions,
#     apparently by an as-yet unknown cytoplasmic ATP-driven component.
#     (For now, just annotate it as another fruA)
# FruA/FruI, where FruI has I-Hpr-IIA components
#   P. aeruginosa has FruA and "FruI"
#   Azospirillum brasilense: FruA = uniprot:G8B0J2 (not yet reannotated) and FruI = AZOBR_RS32325
#  	(curated, but definition line does not mention fructose, so was not originally included)
#   Xanthomonas campestris: FruA = P23355 and FruI = XCC2370 = P45597

fruA	fructose-specific PTS system (fructose 1-phosphate forming), EII-B'BC components	curated:BRENDA::Q8DWE7	curated:SwissProt::P20966	curated:SwissProt::P23355	ignore:TCDB::P32154	curated:TCDB::Q9HY57	curated:TCDB::Q9RZP7	uniprot:G8B0J2

# Homologs of fruB from Salmonella typhimurium and Haemophilus influenzae probably have the
# same function, but are annotated differently in SwissProt.
fruB	fructose-specific PTS system (fructose 1-phosphate forming), Hpr and EII-A components	curated:SwissProt::P69811	ignore:SwissProt::P17127	ignore:SwissProt::P44715

# Homologs of fruI in other Pseudomonas fluorescens are annotated differently, but
# are important for fructose utilization, so probably have the same function.
fruI	fructose-specific PTS system (fructose 1-phosphate forming), EI, Hpr, and EII-A components	curated:TCDB::Q9HY55	curated:reanno::azobra:AZOBR_RS32325	curated:reanno::pseudo3_N2E3:AO353_05485	curated:SwissProt::P45597	curated:reanno::pseudo1_N1B4:Pf1N1B4_1146	curated:reanno::pseudo5_N2C3_1:AO356_07335	curated:reanno::WCS417:GFF780	curated:reanno::psRCH2:GFF3291

# Streptococcus mutans has FruA-like "FruC" plus "FruD" with EII-A only.
fruD	fructose-specific PTS system (fructose 1-phosphate forming), EII-A component	curated:BRENDA::Q8DWE6

# Fructose 1-phosphate forming PTS systems contain FruA with either FruB, FruI, or FruD.
# FruA has EII-B'BC components; the other genes all have E-IIA but their domain content varies.
# FruB has E-IIA and Hpr components; FruI has EI-Hpr-IIA components; and FruD has E-IIA only.
fructose-PTS-1-phosphate: fruA fruB
fructose-PTS-1-phosphate: fruA fruI
fructose-PTS-1-phosphate: fruA fruD

# 3-part PTS system (fructose 1-phosphate forming) in Haloferax volcanii, Haloterrigena turkmenica, Haloarcula marismortui.
# The Haloarcula gene cluster also includes enzyme I (ptsI, Q5V5X2) and HPr (ptsH, Q5V5X3),
# which is not represented here
fruII-A	fructose-specific PTS system (fructose 1-phosphate forming), EII-A component	curated:TCDB::D2RXA7	curated:SwissProt::D4GYE4	curated:TCDB::Q5V5X4
fruII-B	fructose-specific PTS system (fructose 1-phosphate forming), EII-B component	curated:SwissProt::D4GYE1	curated:TCDB::D2RXA4	curated:TCDB::Q5V5X1
fruII-C	fructose-specific PTS system (fructose 1-phosphate forming), EII-C component	curated:SwissProt::D4GYE5	curated:TCDB::D2RXA8	curated:TCDB::Q5V5X5
fructose-PTS-1-phosphate: fruII-A fruII-B fruII-C

# Spiroplasma citri has a unified PTS system E-IIABC which clustered with fruA above but is distantly related
# The others were in cluster 4
fruII-ABC	fructose-specific PTS system (fructose 1-phosphate forming), EII-ABC components	curated:TCDB::Q9RMF5	curated:TCDB::Q3K0G6	curated:TCDB::P71012	curated:TCDB::Q0S1N2	curated:TCDB::Q1LZ59
fructose-PTS-1-phosphate: fruII-ABC

# Fructose 6-phosphate forming PTS systems, which are all of the "mannose" type
# and have an additional EII-D component.
# B. subtilis has 4 components (levDEFG, also known as ptfABCD)
# while in E. coli, Oneococcus oeni, and Streptococcus thermophilus, the EII-AB components are fused

levD	fructose PTS system (fructose 6-phosphate forming), EII-A component	curated:SwissProt::P26379
levE	fructose PTS system (fructose 6-phosphate forming), EII-B component	curated:SwissProt::P26380

# uniprot:Q9S4L5 is nearly identical to uniprot:Q5M5W6; not sure if it acts on fructose or not.
# uniprot:D2BKY7 is very similar to uniprot:Q5M5W6 and has been studied mostly as a receptor to bacteriocins; not
#   sure if it acts on fructose or not.
levDE	fructose PTS system (fructose 6-phosphate forming), EII-AB component	curated:CharProtDB::CH_088329	curated:TCDB::Q04GK1	curated:TCDB::Q5M5W6	ignore:BRENDA::Q9S4L5	ignore:TCDB::D2BKY7

levF	fructose PTS system (fructose 6-phosphate forming), EII-C component	curated:CharProtDB::CH_088330	curated:TCDB::P26381	curated:TCDB::Q04GK0	curated:TCDB::Q5M5W7

# Ignore SwissProt::P69805 which is nearly identical to P69805.
# Ignore Q5IRC0, whose specificity is unknown.
levG	fructose PTS system (fructose 6-phosphate forming), EII-D component	curated:TCDB::P26382	curated:TCDB::P69805	curated:TCDB::Q04GJ9	curated:TCDB::Q5M5W8	ignore:SwissProt::P69805	ignore:BRENDA::Q5IRC0

fructose-PTS-6-phosphate: levD levE levF levG
fructose-PTS-6-phosphate: levDE levF levG

# ABC type transporters

# AraSUTV from Sulfolobus solfataricus
araV	fructose ABC transporter, ATPase component AraV	curated:TCDB::Q97UF2
araU	fructose ABC transporter, permease component 1 (AraU)	curated:TCDB::Q97UF3
araT	fructose ABC transporter, permease component 2 (AraT)	curated:TCDB::Q97UF4
araS	fructose ABC transporter, substrate-binding component AraS	curated:TCDB::Q97UF5

# Transporters and PTS systems (forming -1-phosphate or -6-phosphate) were found using
# query: transporter:fructose:D-fructose:BETA-D-FRUCTOSE.
fructose-transport: araV araU araT araS

# FruEFGK from Bifidobacterium longum.
# (FruF is distantly related to frcC, which is described separately)
fruE	fructose ABC transporter, substrate-binding component FruE	curated:SwissProt::Q8G848
fruF	fructose ABC transporter, permease component 1 (FruF)	curated:SwissProt::Q8G846
fruG	fructose ABC transporter, permease component 2 (FruG)	curated:SwissProt::Q8G845
fruK	fructose ABC transporter, ATPase component FruK	curated:SwissProt::Q8G847
fructose-transport: fruE fruF fruG fruK

# FrcABC from Rhizobium meliloti.
# A distantly related system in Ralstonia eutropha H16 is required for fructose utilization (PMID:21478317),
# and fitness data confirms that the homologs in Cupriavidus basilensis 4G11 are
# important during growth on fructose
# (frcA = RR42_RS03360 = A0A0C4Y5F6; frcC = RR42_RS03365 = A0A0C4Y7K0; frcB = RR42_RS03370 = A0A0C4Y591)
frcA	fructose ABC transporter, ATPase component FrcA	curated:SwissProt::Q9F9B0	uniprot:A0A0C4Y5F6
frcB	fructose ABC transporter, substrate-binding component FrcB	curated:SwissProt::Q9F9B2	uniprot:A0A0C4Y591
frcC	fructose ABC transporter, permease component FrcC	curated:SwissProt::Q9F9B1	uniprot:A0A0C4Y7K0
fructose-transport: frcA frcB frcC

# Homomeric transporters:

# Ignore Q6PXP3 (GTR7_HUMAN) as there is debate as to its activity
Slc2a5	fructose:H+ symporter	curated:TCDB::A0ZXK6	curated:CharProtDB::CH_091463	curated:SwissProt::P22732	curated:SwissProt::P43427	curated:SwissProt::P46408	curated:SwissProt::P58353	ignore:SwissProt::Q6PXP3	curated:SwissProt::Q9WV38	curated:TCDB::Q9XIH7
fructose-transport: Slc2a5

ffz	fructose facilitator (uniporter)	curated:TCDB::C5DX43	curated:TCDB::C5E4Z7	curated:TCDB::Q70WR7
fructose-transport: ffz

glcP	fructose:H+ symporter GlcP	curated:TCDB::P15729	curated:reanno::Korea:Ga0059261_1777
fructose-transport: glcP

ght6	high-affinity fructose transporter ght6	curated:CharProtDB::CH_091085
fructose-transport: ght6

STP6	sugar transport protein 6	curated:CharProtDB::CH_091493
fructose-transport: STP6

THT2A	fructose THT2A	curated:TCDB::Q06222
fructose-transport: THT2A

frt1	fructose:H+ symporter Frt1	curated:TCDB::Q8NJ22
fructose-transport: frt1

# N515DRAFT_1918 (A0A1I2JXG1) from Dyella japonica UNC79MFTsu3.2 is an MFS-type transporter that is
# specifically important for growth on fructose.
fruP	fructose porter FruP	uniprot:A0A1I2JXG1
fructose-transport: fruP

# The putative hexose transporter BT1758 (Q8A6W8) is important for fructose and levan utilization
# It is in a fructan utilization cluster, so was propsoed to be the fructose transporter (see PMC3225772)
BT1758	fructose transporter	uniprot:Q8A6W8
fructose-transport: BT1758

# Ignore CharProtDB::CH_122687,  potential proton-coupled fructose symporter from Candida albicans,
# not actually characterized

# Ignore the fructose porin (TCDB::Q51485, 1.B.19.1.1) from Pseudomonas aeruginosa

# For a PTS forming fructose 6-phosphate, no further steps are needed to reach
# central metabolism.
fructose-utilization: fructose-PTS-6-phosphate

# ignore fragmentary sequence of Q09123
scrK	fructokinase	EC:	ignore:SwissProt::Q09123

# For direct transport, the usual pathway is fructokinase (scrK), forming fructose 6-phosphate.
fructose-utilization: fructose-transport scrK

1pfk	1-phosphofructokinase	EC:

# Ignore several fragmentary sequences, and CH_091808 seems to be misannotated with another EC number
# Q5SJM8 is nearly identical to Q72K02, a bifunctional aldolase/phosphatase, but is annotated only as phosphatase
fba	fructose 1,6-bisphosphate aldolase	EC:	ignore:SwissProt::P84722	ignore:SwissProt::P86979	ignore:SwissProt::P86980	ignore:CharProtDB::CH_091808	ignore:BRENDA::Q5SJM8

# Ignore a fragmentary (allergen) sequence
tpi	triose-phosphate isomerase	EC:	ignore:SwissProt::P85814

# For PTS forming fructose 1-phosphate, the usual path is phosphorylation (1pfk) and
# cleavage by fructose 1,6-bisphosphate aldolase (fba); triose-phosphate isomerase (tpi)
# converts the glycerone phosphate to D-glyceraldehyde 3-phosphate, which is
# a central metabolic intermediate.
fructose-utilization: fructose-PTS-1-phosphate 1pfk fba tpi

all: fructose-utilization



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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:

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:

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:

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, or view the source code.

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