D-cellobiose catabolism in Klebsiella michiganensis M5al

GapMind for catabolism of small carbon sources

D-cellobiose catabolism in Klebsiella michiganensis M5al

Best path

Also see fitness data for the top candidates

Rules

Overview: MetaCyc does not list any pathways for cellobiose utilization, but the major catabolic enzymes are believed to be intracellular cellobiase, periplasmic cellobiase, cellobiose-6-phosphate hydrolase, or cellobiose phosphorylase (PMID:28535986). These pathways all lead to glucose-6-phosphate, which is a central metabolic intermediate. There also may be a 3-ketoglucoside pathway in some Bacteroidetes, but this is not characterized.

all:

bgl and glucose-utilization
or cellobiose-transport, bgl and glk
or cellobiose-transport, cbp, pgmA and glk
or cellobiose-PTS, ascB and glk
Comment: Cellobiose may be cleaved to two glucose in the periplasm (by bgl). Or, after transport, cellobiose may be cleaved in the cytoplasm and then the glucose is phosphorylated by glk. Or cellobiose is cleaved by cellobiose phosphorylase (cbp), into glucose and alpha-glucose-1-phosphate; alpha-phosphoglucomutase (pgmA) converts the glucose-1-P to glucose-6-phosphate and glucokinase converts glucose to glucose-6-phosphate. Or, after transport and phosphorylation by a PTS system, 6-phosphocellobiose hydrolase forms glucose and glucose-6-phosphate, and glucokinase converts the glucose to glucose-6-phosphate.

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

cellobiose-PTS:

bglG
or celEIIA, celEIIB and celEIIC

cellobiose-transport:

TM0031, TM0030, TM0029, TM0028 and TM0027
or cbtA, cbtB, cbtC, cbtD and cbtF
or cebE, cebF, cebG and msiK
or SMc04256, SMc04257, SMc04258 and SMc04259
or cbpB, msdB1 and msdB2
or cbpC, msdC1 and msdC2
or cdt
or bglT
Comment: Transporters and PTS systems were identified uing query: transporter:cellobiose:D-cellobiose:CPD-15976:beta-glucoside:beta-glucosides. But, some of the beta-glucoside transporters might not be cellobiose transporters. Omitted TCDB 4.A.1.2.15 = LGAS_1755 = ART98417 (see curated BLAST for PTS vs. GCF_000014425.1), "PTS 19CBA" in PMC2848229 (Francl et al 2010); this was not actually shown to be a cellobiose transporter (and, the main one in this organism is TC 4.A.1.2.14 = LGAS_1669). Omitted TM1219:TM1223, listed as a probable cellobiose porter: the SBP TM1223 is reported to bind beta,1-4-mannobiose only (PMC1392961).

73 steps (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
bgl	cellobiase	BWI76_RS19510	BWI76_RS11890
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'	glucose ABC transporter, substrate-binding component (AglE)
aglF'	glucose ABC transporter, permease component 1 (AglF)	BWI76_RS03135
aglG'	glucose ABC transporter, permease component 2 (AglG)	BWI76_RS01820
aglK'	glucose ABC transporter, ATPase component (AglK)	BWI76_RS01840	BWI76_RS06690
ascB	6-phosphocellobiose hydrolase	BWI76_RS19550	BWI76_RS23855
bglF	glucose PTS, enzyme II (BCA components, BglF)	BWI76_RS19555	BWI76_RS07290
bglG	cellobiose PTS system, EII-BC or EII-BCA components	BWI76_RS22290	BWI76_RS19555
bglT	cellobiose transporter BglT	BWI76_RS27490	BWI76_RS27595
cbp	cellobiose phosphorylase
cbpB	cellobiose ABC transporter, substrate-binding component CpbB
cbpC	cellobiose ABC transporter, substrate-binding component CbpC
cbtA	cellobiose ABC transporter, substrate-binding component CbtA
cbtB	cellobiose ABC transporter, permease component 1 (CbtB)
cbtC	cellobiose ABC transporter, permease component 2 (CbtC)
cbtD	cellobiose ABC transporter, ATPase component 1 (CbtD)	BWI76_RS26870	BWI76_RS17225
cbtF	cellobiose ABC transporter, ATPase component 2 (CbtF)	BWI76_RS26865	BWI76_RS17220
cdt	cellobiose transporter cdt-1/cdt-2
cebE	cellobiose ABC transporter, substrate-binding component CebE
cebF	cellobiose ABC transporter, permease component 1 (CebF)	BWI76_RS23380	BWI76_RS03135
cebG	cellobiose ABC transporter, permease component 2 (CebG)	BWI76_RS17835	BWI76_RS26295
celEIIA	cellobiose PTS system, EII-A component	BWI76_RS11735	BWI76_RS22410
celEIIB	cellobiose PTS system, EII-B component	BWI76_RS11725	BWI76_RS01520
celEIIC	cellobiose PTS system, EII-C component	BWI76_RS11730	BWI76_RS14945
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
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
msdB1	cellobiose ABC transporter, permease component 1 (MsdB1)
msdB2	cellobiose ABC transporter, permease component 2 (MsdB2)
msdC1	cellobiose ABC transporter, permease component 1 (MsdC1)	BWI76_RS17840	BWI76_RS03135
msdC2	cellobiose ABC transporter, permease component 1 (MsdC2)	BWI76_RS23385
msiK	cellobiose ABC transporter, ATPase component	BWI76_RS26290	BWI76_RS17830
PAST-A	proton-associated sugar transporter A
pgmA	alpha-phosphoglucomutase	BWI76_RS08290	BWI76_RS25130
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
SMc04256	cellobiose ABC transporter, ATPase component	BWI76_RS26290	BWI76_RS06690
SMc04257	cellobiose ABC transporter, permease component 1
SMc04258	cellobiose ABC transporter, permease component 2
SMc04259	cellobiose ABC transporter, substrate-binding protein
SSS-glucose	Sodium/glucose cotransporter
SWEET1	bidirectional sugar transporter SWEET1
TM0027	cellobiose ABC transporter, ATPase component 2	BWI76_RS07535	BWI76_RS12010
TM0028	cellobiose ABC transporter, ATPase component 1	BWI76_RS07535	BWI76_RS17225
TM0029	cellobiose ABC transporter, permease component 2
TM0030	cellobiose ABC transporter, permease component 1	BWI76_RS07525	BWI76_RS19200
TM0031	cellobiose ABC transporter, substrate-binding component

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)
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SQLite3 databases

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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