trehalose catabolism in Klebsiella michiganensis M5al

GapMind for catabolism of small carbon sources

trehalose catabolism in Klebsiella michiganensis M5al

Best path

Also see fitness data for the top candidates

Rules

Overview: Trehalose degradation is based on MetaCyc pathways I via trehalose-6-phosphate hydrolase (link), II via cytoplasmic trehalase (link), III via trehalose-6-phosphate phosphorylase (link), IV via inverting trehalose phosphorylase (link), V via trehalose phosphorylase (link), VI via periplasmic trehalase (link), as well as trehalose degradation via 3-ketotrehalose (PMID:33657378).

all:

trehalose-3-dehydrogenase, klh and glucose-utilization
or treF and glucose-utilization
or trehalose-PTS, treC and glk
or trehalose-transport, treF and glk
or trehalose-PTS, trePP and pgmB
or trehalose-transport, treP, pgmB and glk
or trehalose-transport, PsTP, pgmA and glk
Comment: 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. In pathway VI, a periplasmic trehalase forms glucose, which is utilized. 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. In pathway II, a cytoplasmic trehalase cleaves trehalose to two glucose, followed by phosphorylation by glk. 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. 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. 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.)

trehalose-3-dehydrogenase:

BT2158
or lacA, lacC and lacB

glucose-utilization:

glucose-transport and glk
or glucose-PTS
or gdh, gnl, gadh1, gadh2, gadh3, kguT, kguK, kguD, edd and eda
Comment: Glucose can be taken up and then phosphorylated to glucose 6-phosphate by the kinase glk. Or, both uptake and phosphorylation are catalyzed by a PTS system. Or, glucose is oxidized to glucono-1,5-lactone in the periplasm (by gdh), hydrolyzed to gluconate (by gnl), oxidized to 2-ketogluconate (by gadh123), taken up by kguT, phosphorylated to 2-dehydro-6-phosphogluconate (by kguK), reduced to gluconate 6-phosphate (by kguD), dehydrated by edd to 2-dehydro-3-deoxy-gluconate 6-phosphate, and cleaved by aldolase eda to pyruvate and D-glyceraldehyde 3-phosphate.

glucose-PTS:

ptsG-crr
or bglF
or ptsG and crr
or manX, manY and manZ

glucose-transport:

MFS-glucose
or SSS-glucose
or glcU'
or PAST-A
or SemiSWEET
or SWEET1
or mglA, mglB and mglC
or gtsA, gtsB, gtsC and gtsD
or glcS, glcT, glcU and glcV
or aglE', aglF', aglG' and aglK'
Comment: Transporters and PTS systems were analyzed uzing query: transporter:glucose:D-glucose:D-glucopyranose:ALPHA-GLUCOSE:GLC:CPD-15374

trehalose-transport:

thuE, thuF, thuG and thuK
or lpqY, thuF, thuG and thuK
or malE2, malF1, malG1 and thuK
or malF, malG, malK and malX
or treS, treT, treU and treV
or aglE, aglF, aglG and aglK
or TRET1
Comment: Transporters and PTS systems were identified using query: transporter:trehalose:D-trehalose

trehalose-PTS: treEIIA and treB

Comment: 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.

74 steps (46 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
treF	trehalase	BWI76_RS26700	BWI76_RS17700
mglA	glucose ABC transporter, ATP-binding component (MglA)	BWI76_RS19640	BWI76_RS07240
mglB	glucose ABC transporter, substrate-binding component	BWI76_RS19645	BWI76_RS27030
mglC	glucose ABC transporter, permease component (MglC)	BWI76_RS19635	BWI76_RS14865
glk	glucokinase	BWI76_RS20510	BWI76_RS22415
Alternative steps:
aglE	trehalose ABC transporter, substrate-binding component AglE
aglE'	glucose ABC transporter, substrate-binding component (AglE)
aglF	trehalose ABC transporter, permease component 1 (AglF)	BWI76_RS03135
aglF'	glucose ABC transporter, permease component 1 (AglF)	BWI76_RS03135
aglG	trehalose ABC transporter, permease component 2 (AglG)	BWI76_RS17835	BWI76_RS06705
aglG'	glucose ABC transporter, permease component 2 (AglG)	BWI76_RS01820
aglK	trehalose ABC trehalose, ATPase component AglK	BWI76_RS01840	BWI76_RS06690
aglK'	glucose ABC transporter, ATPase component (AglK)	BWI76_RS01840	BWI76_RS06690
bglF	glucose PTS, enzyme II (BCA components, BglF)	BWI76_RS19555	BWI76_RS07290
BT2158	periplasmic trehalose 3-dehydrogenase (BT2158)
crr	glucose PTS, enzyme IIA	BWI76_RS20655	BWI76_RS08220
eda	2-keto-3-deoxygluconate 6-phosphate aldolase	BWI76_RS18095	BWI76_RS27940
edd	phosphogluconate dehydratase	BWI76_RS18100	BWI76_RS00975
gadh1	gluconate 2-dehydrogenase flavoprotein subunit
gadh2	gluconate 2-dehydrogenase cytochrome c subunit
gadh3	gluconate 2-dehydrogenase subunit 3
gdh	quinoprotein glucose dehydrogenase	BWI76_RS04950	BWI76_RS13270
glcS	glucose ABC transporter, substrate-binding component (GlcS)
glcT	glucose ABC transporter, permease component 1 (GlcT)
glcU	glucose ABC transporter, permease component 2 (GlcU)
glcU'	Glucose uptake protein GlcU
glcV	glucose ABC transporter, ATPase component (GclV)	BWI76_RS09465	BWI76_RS06035
gnl	gluconolactonase	BWI76_RS23720	BWI76_RS21470
gtsA	glucose ABC transporter, substrate-binding component (GtsA)
gtsB	glucose ABC transporter, permease component 1 (GtsB)	BWI76_RS23380
gtsC	glucose ABC transporter, permease component 2 (GtsC)	BWI76_RS17835	BWI76_RS06705
gtsD	glucose ABC transporter, ATPase component (GtsD)	BWI76_RS03270	BWI76_RS06690
kguD	2-keto-6-phosphogluconate reductase	BWI76_RS26960	BWI76_RS27925
kguK	2-ketogluconokinase	BWI76_RS26950	BWI76_RS07325
kguT	2-ketogluconate transporter	BWI76_RS26955	BWI76_RS06145
klh	3-ketotrehalose hydrolase
lacA	periplasmic trehalose 3-dehydrogenase, LacA subunit
lacB	periplasmic trehalose 3-dehydrogenase, cytochrome c subunit (LacB)
lacC	periplasmic trehalose 3-dehydrogenase, LacC subunit
lpqY	trehalose ABC transporter, substrate-binding lipoprotein component LpqY
malE2	trehalose ABC transporter, substrate-binding component MalE2	BWI76_RS01830	BWI76_RS06695
malF	trehalose ABC transporter, permease component 1 (MalF)	BWI76_RS03245	BWI76_RS06700
malF1	trehalose ABC transporter, permease component 1	BWI76_RS01825
malG	trehalose ABC transporter, permease component 2 (MalG)	BWI76_RS03240	BWI76_RS06705
malG1	trehalose ABC transporter, permease component 2 (MalG1/MalG2)
malK	trehalose ABC transporter, ATPase component MalK	BWI76_RS03270	BWI76_RS23390
malX	trehalose ABC transporter, substrate-binding component MalX
manX	glucose PTS, enzyme EIIAB	BWI76_RS17890	BWI76_RS01735
manY	glucose PTS, enzyme EIIC	BWI76_RS17895	BWI76_RS01730
manZ	glucose PTS, enzyme EIID	BWI76_RS17900	BWI76_RS01725
MFS-glucose	glucose transporter, MFS superfamily	BWI76_RS24055	BWI76_RS17580
PAST-A	proton-associated sugar transporter A
pgmA	alpha-phosphoglucomutase	BWI76_RS08290	BWI76_RS25130
pgmB	beta-phosphoglucomutase	BWI76_RS11780
PsTP	trehalose phosphorylase
ptsG	glucose PTS, enzyme IICB	BWI76_RS11130	BWI76_RS08220
ptsG-crr	glucose PTS, enzyme II (CBA components, PtsG)	BWI76_RS11130	BWI76_RS08220
SemiSWEET	Sugar transporter SemiSWEET
SSS-glucose	Sodium/glucose cotransporter
SWEET1	bidirectional sugar transporter SWEET1
thuE	trehalose ABC transporter, substrate-binding component ThuE
thuF	trehalose ABC transporter, permease component 1 (ThuF)	BWI76_RS23380	BWI76_RS17840
thuG	trehalose ABC transporter, permease component 2 (ThuG)	BWI76_RS03240	BWI76_RS01820
thuK	trehalose ABC transporter, ATPase component ThuK	BWI76_RS03270	BWI76_RS23390
treB	trehalose PTS system, EII-BC components TreB	BWI76_RS02965	BWI76_RS07315
treC	trehalose-6-phosphate hydrolase	BWI76_RS02960	BWI76_RS16585
treEIIA	N-acetylglucosamine phosphotransferase system, EII-A component (Crr/PtsG/YpqE/GamP)	BWI76_RS20655	BWI76_RS08220
treP	trehalose phosphorylase, inverting
trePP	trehalose-6-phosphate phosphorylase
treS	trehalose ABC transporter, substrate-binding comopnent TreS
treT	trehalose ABC transporter, permease component 1 (TreT)	BWI76_RS26300
TRET1	facilitated trehalose transporter Tret1	BWI76_RS24055	BWI76_RS23425
treU	trehalose ABC transporter, permease component 2 (TreU)
treV	trehalose ABC transporter, ATPase component TreV	BWI76_RS06690	BWI76_RS26290

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 17 2021. The underlying query database was built on Sep 17 2021.

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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