GapMind for catabolism of small carbon sources


Definition of trehalose catabolism

As text, or see rules and steps

# Trehalose degradation is based on MetaCyc pathways
# I via trehalose-6-phosphate hydrolase (metacyc:TREDEGLOW-PWY),
# II via cytoplasmic trehalase (metacyc:PWY0-1182),
# III via trehalose-6-phosphate phosphorylase (metacyc:PWY-2721),
# IV via inverting trehalose phosphorylase (metacyc:PWY-2722),
# V via trehalose phosphorylase (metacyc:PWY-2723),
# VI via periplasmic trehalase (metacyc:PWY0-1466),
# as well as trehalose degradation via 3-ketotrehalose (PMID:33657378).

treB	trehalose PTS system, EII-BC components TreB	curated:BRENDA::P36672	curated:SwissProt::P39794	curated:TCDB::Q720G7	uniprot:A0A0N9WDQ5	uniprot:A0A1N7UR85	curated:BRENDA::A0A0H3F7X9

# Ignore a close homlog in Serratia (TC 4.A.3.2.5 / Q8L3C4) which is reported to be the II-A component,
# and the homolog in Salmonella. Include E. coli crr and B. subtilis ptsG, gamP, or ptsA (PMC6148471).
treEIIA	N-acetylglucosamine phosphotransferase system, EII-A component (Crr/PtsG/YpqE/GamP)	curated:TCDB::P20166	uniprot:P50829	curated:SwissProt::P39816	curated:CharProtDB::CH_088352	ignore:SwissProt::P0A283	ignore:TCDB::Q8L3C4	curated:reanno::WCS417:GFF4500	curated:reanno::pseudo3_N2E3:AO353_15995

# PTS systems form trehalose 6-phosphate.
# E. coli has EII-BC treB; crr is the EII-A.
# B. subtilis has EII-BC treP. PMC6148471 shows that ptsG is the predominant EII-A but gamP and ptsA also function.
# Listeria monocytogenes has EII-BC; the EII-A is not known.
# Pseudomonas simiae WCS417 and P. fluorescens FW300-N2E3 have similar systems
# but only EII-A is annotated. In FW300-N2E3, AO353_15980 (A0A0N9WDQ5) is the II-BC protein.
# In WCS417, PS417_23050 (A0A1N7UR85) is the II-BC protein. These are both similar to E. coli treB.
trehalose-PTS: treEIIA treB

# ABC transporters:

# Sinorhizobium meliloti has two distantly related systems: trehalose-inducible thuEFGK
#   and sucrose-inducible aglEFGK

# Systems similar to thuEFGK from Sinorhizobium meliloti
# are also found in Thermotoga maritima, Thermus thermophilus and Thermococcus litoralis.
# (The ATPase component in T. maritima is not described.)
# Mycobacterium tuberculosis has a similar system with a diverged SBP.
# A system similar to that from T. thermophilus, in Pyrococcus furiosus, also transports trehalose (PMC2685544).
thuE	trehalose ABC transporter, substrate-binding component ThuE	curated:TCDB::G4FGN8	curated:TCDB::O51923	curated:TCDB::Q72H68	curated:TCDB::Q9R9Q7	curated:SwissProt::Q7LYW7

# (Removed Sulfolobus treT, which is related but is described separately)
thuF	trehalose ABC transporter, permease component 1 (ThuF)	curated:SwissProt::O51924	curated:SwissProt::P9WG03	curated:TCDB::G4FGN7	curated:TCDB::O51924	curated:TCDB::Q72H67	curated:reanno::Smeli:SM_b20326

thuG	trehalose ABC transporter, permease component 2 (ThuG)	curated:SwissProt::Q7LYX6	curated:SwissProt::P9WG01	curated:TCDB::G4FGN6	curated:TCDB::Q72H66	curated:reanno::Smeli:SM_b20327

thuK	trehalose ABC transporter, ATPase component ThuK	curated:SwissProt::P9WQI3	curated:SwissProt::Q9YGA6	curated:TCDB::Q72L52	curated:TCDB::Q9R9Q4	curated:TCDB::Q9X103	

# Transporters and PTS systems were identified using
# query: transporter:trehalose:D-trehalose
trehalose-transport: thuE thuF thuG thuK

lpqY	trehalose ABC transporter, substrate-binding lipoprotein component LpqY	curated:SwissProt::P9WGU9

trehalose-transport: lpqY thuF thuG thuK

# Thermotoga maritima also has  TC 3.A.1.1.22 system with two different SBPs (malE1E2) and also malF1G1G2K
# These are duplicated operons and probably either paralog will work with either SBP.
# Only malE2 binds trehalose (PMC1064059).
# The ATPase component (malK) is quite similar to thuK and was included in that definition
malE2	trehalose ABC transporter, substrate-binding component MalE2	curated:TCDB::Q9S5Y1
malF1	trehalose ABC transporter, permease component 1	curated:TCDB::Q9X0T0
malG1	trehalose ABC transporter, permease component 2 (MalG1/MalG2)	curated:BRENDA::Q9X0S9	curated:BRENDA::Q9X2F5
trehalose-transport: malE2 malF1 malG1 thuK

# Streptococcus mutans malXFGK
malF	trehalose ABC transporter, permease component 1 (MalF)	curated:TCDB::Q8DT27
malG	trehalose ABC transporter, permease component 2 (MalG)	curated:TCDB::Q8DT26
# The related ATPase msmK can substitute for malK (PMC2223742)
malK	trehalose ABC transporter, ATPase component MalK	curated:TCDB::Q8DT25	curated:TCDB::Q00752
malX	trehalose ABC transporter, substrate-binding component MalX	curated:TCDB::Q8DT28
trehalose-transport: malF malG malK malX

# Sulfolobus solfataricus treSTUV
treS	trehalose ABC transporter, substrate-binding comopnent TreS	curated:TCDB::Q97ZC3
treT	trehalose ABC transporter, permease component 1 (TreT)	curated:TCDB::Q97ZC2
treU	trehalose ABC transporter, permease component 2 (TreU)	curated:TCDB::Q97ZC1
treV	trehalose ABC transporter, ATPase component TreV	curated:TCDB::Q97ZC0
trehalose-transport: treS treT treU treV

# S. meliloti aglEFGK.
# A similar system from Dinoroseobacter shibae, Dshi_1652:Dshi_1648, is involved in maltose uptake.
# Dinoroseobacter shibae aglE = Dshi_1652 = A8LLL6.
# Ignore similarity to Slr0529, which may also transport trehalose
aglE	trehalose ABC transporter, substrate-binding component AglE	curated:TCDB::Q9Z3R5	uniprot:A8LLL6	ignore:TCDB::Q55471

# Dinoroseobacter shibae aglF = Dshi_1651 = A8LLL5.
aglF	trehalose ABC transporter, permease component 1 (AglF)	curated:reanno::Smeli:SMc03062	uniprot:A8LLL5

# Dinoroseobacter shibae aglG = Dshi_1650 = A8LLL4.
aglG	trehalose ABC transporter, permease component 2 (AglG)	curated:reanno::Smeli:SMc03063	uniprot:A8LLL4

# Dinoroseobacter shibae aglK = Dshi_1648 = A8LLL2.
aglK	trehalose ABC trehalose, ATPase component AglK	curated:reanno::Smeli:SMc03065	uniprot:A8LLL2

trehalose-transport: aglE aglF aglG aglK

# For the system in Bdellovibrio bacteriovorus, just one protein (fused MalEF) seems to have been studied,
#   and did not have access to the paper, so did not include.

# Streptomyces coelicolor has agl3EFG; although expression is induced by trehalose, its function
# remains uncertain, so it is not described here

TRET1	facilitated trehalose transporter Tret1	curated:SwissProt::A5LGM7	curated:SwissProt::A9ZSY2	curated:SwissProt::A9ZSY3	curated:SwissProt::Q8MKK4
trehalose-transport: TRET1

# Tret1-1 has a very high Km so is not included

import glucose.steps:glucose-utilization glk

BT2158	periplasmic trehalose 3-dehydrogenase (BT2158)	curated:reanno::Btheta:351686

# These gene names are from the homologous system in Caulobacter crescentus, which is required for
# lactose utilization; but Caulobacter crescentus does not grow with trehalose as the sole
# source of carbon, and Caulobacter LacACB may not be active on trehalsoe.
lacA	periplasmic trehalose 3-dehydrogenase, LacA subunit	curated:reanno::Pedo557:CA265_RS15345	curated:reanno::Cola:Echvi_1847	ignore_other:
lacC	periplasmic trehalose 3-dehydrogenase, LacC subunit	curated:reanno::Pedo557:CA265_RS15340	curated:reanno::Cola:Echvi_1848	ignore_other:
lacB	periplasmic trehalose 3-dehydrogenase, cytochrome c subunit (LacB)	curated:reanno::Pedo557:CA265_RS15360	curated:reanno::Cola:Echvi_1841	ignore_other:

trehalose-3-dehydrogenase: BT2158
trehalose-3-dehydrogenase: lacA lacC lacB

# BT2157 (351686) is required for utilization of trehalose (or 3-ketotrehalose) and
# hydrolyzes 3-ketotrehalose. CA265_RS22975 and Echvi_2921 are similar proteins that are
# involved in trehalose utilization.
klh	3-ketotrehalose hydrolase	curated:reanno::Btheta:351685	curated:reanno::Pedo557:CA265_RS22975	curated:reanno::Cola:Echvi_2921

# In the 3-ketotrehalose pathway, a periplasmic dehydrogenase forms 3-ketotrehalose,
# a periplasmic 3-ketoglycoside hydrolase (klh) forms glucose and 3-ketoglucose,
# and the glucose is taken up and utilized;
# the fate of the 3-ketoglucose is not well understood, but its utilization might not be necessary.
all: trehalose-3-dehydrogenase klh glucose-utilization

# PGA1_c07890 (I7EUW4) is important for trehalose and cellobiose utilization (it is probably cytoplasmic).
# Dshi_1649 from Dinoroseobacter shibae (A8LLL3) is important for trehalose utilization.
treF	trehalase	EC:	uniprot:I7EUW4	uniprot:A8LLL3

# In pathway VI, a periplasmic trehalase forms glucose, which is utilized.
all: treF glucose-utilization

treC	trehalose-6-phosphate hydrolase	EC:

# In pathway I, after uptake and phosphorylation by the PTS,
# trehalose 6-phosphate hydrolase (treC) forms D-glucose 6-phosphate and D-glucose,
# and glucokinase (glk) phosphorylates the glucose.
all: trehalose-PTS treC glk

# In pathway II, a cytoplasmic trehalase cleaves trehalose to two glucose,
# followed by phosphorylation by glk.
all: trehalose-transport treF glk

trePP	trehalose-6-phosphate phosphorylase	EC:
pgmB	beta-phosphoglucomutase	EC:

# In pathway III, after uptake and phosphorylation by the PTS,
# trehalose-6-phosphate phosphorylase (trePP) forms beta-glucose-1-phosphate and glucose-6-phosphate,
# and beta-phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate.
all: trehalose-PTS trePP pgmB

# Forms beta-glucose 1-phosphate and glucose.
# CA265_RS24655 is misannotated as a trehalose phosphorylase (the fitness data actually confirms
# that it is a maltose phosphorylase).
treP	trehalose phosphorylase, inverting	EC:	ignore:reanno::Pedo557:CA265_RS24655

# In pathway IV, a secreted inverting trehalose phoshorylase (treP) forms beta-glucose 1-phosphate and glucose;
# the beta-D-glucose is consumed by beta-phosphoglucomutase.
all: trehalose-transport treP pgmB glk

PsTP	trehalose phosphorylase	EC:
import galactose.steps:pgmA

# In pathway V, trehalose phosphorylase forms alpha-glucose-1-phosphate and glucose;
# these are converted to glucose-6-P by alpha-phosphoglucomutase (pgmA) and glk.
# (This is a fungal pathway and might not occur in prokaryotes.)
all: trehalose-transport PsTP pgmA glk



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:

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