lactose catabolism in Cronobacter condimenti 1330

GapMind for catabolism of small carbon sources

lactose catabolism in Cronobacter condimenti 1330

Best path

lacY, lacZ, galK, galT, galE, pgmA, glk

Rules

Overview: Lactose utilization in GapMind is based on MetaCyc pathway lactose degradation II via 3'-ketolactose (link), pathway III via beta-galactosidase (link), or uptake by a PTS system followed by hydrolysis of lactose 6'-phosphate. (There is no pathway I.)

all:

lactose-transport, beta-galactosidase, galactose-degradation and glk
or lactose-PTS, pbgal, galactose-6-phosphate-degradation and glk
or lacA', lacC', lacB', klh and glucose-utilization
Comment: In pathway III, lactose is taken up and cleaved to galactose and glucose by beta-galactosidase; the glucose is consumed by kinase glk. (The galactose 1-epimerase galM, EC 5.1.3.3, is not included in galactose degradation; it is important for lactose utilization in E. coli (PMID:7966338), but not in Sinorhizobium meliloti or in Bacteroides thetaiotaomicron, which also use this pathway.) Or, a PTS forms lactose 6'-phosphate and phosphogalactosidase (pbgal) forms galactose 6-phosphate and glucose. Or, lactose is oxidized to 3'-ketolactose by a periplasmic 3-component dehydrogenase (lacACB'), and then hydrolyzed by a periplasmic enzyme (klh) to 3-keto-beta-D-galactose and D-glucopyranose, and hypothetical reduction of the 3-ketogalactose. Liberation of glucose is probably sufficient for growth.

beta-galactosidase:

lacZ
or lacL and lacM
Comment: Most lactases are homomeric, but Lactobacillus have a heteromeric enzyme LacLM. (There is also a heteromeric beta-galactosidase in barley, see BGAL_HORVU, but it is not included. Also, "evolved beta-galactosidase" ebgA from E. coli is more active with its partner ebgC, but it retains activity on its own, so it is included in step lacZ instead.)

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

galactose-degradation:

galK, galT, galE and pgmA
or galdh, galactonolactonase, dgoD, dgoK and dgoA
Comment: In the Leloir pathway, galactokinase (galK) forms galactose 1-phosphate, a uridyltransferase (galT) uses glucose 1-phosphate to form UDP-galactose, an epimerase (galE) forms UDP-glucose, and this is converted to glucose 1-phosphate by the same uridyltransferase. (We initially included the 1-epimerase galM, EC 5.1.3.3, in our model of the Leloir pathway, but found that in most bacteria, galM proteins were not important for fitness during growth on galactose; the only exception was Echvi_0697.) The oxidative pathway begins with oxidation to a lactone (by galdh) and hydrolysis to galactonate; galactonate is then dehydrated, phosphorylated, and cleaved by an aldolase.

galactose-6-phosphate-degradation: lacA, lacB, lacC, tag16P-aldolase and tpi

Comment: The tagatose 6-phosphate pathway involves the isomerization of galactose 6-phosphate to tagatose-6-phosphate (by lacAB), phosphorylation to tagatose 1,6-bisphosphate (by lacC), and an aldolase.

tag16P-aldolase:

lacD
or gatY and gatZ
Comment: Two forms of D-tagatose-1,6-phosphate aldolase are known, homomeric (lacD) or heteromeric (gatYZ or kbaYZ)

lactose-PTS:

lacIIA, lacIIB and lacIIC
or lacIIA and lacIICB
Comment: PTS systems forming lactose 6'-phosphate. Klebsiella pneumoniae has a EIIA,B,C in three separate proteins. The other characterized PTS systems have EIIA and EIICB

lactose-transport:

lacE, lacF, lacG and lacK
or lacP
or lacS
or lacY
Comment: Transporters and PTS systems were identified using query: transporter:lactose:alpha-lactose:CPD-15971

74 steps (45 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
lacY	lactose:proton symporter LacY	BN137_RS02265	BN137_RS17270
lacZ	lactase (homomeric)	BN137_RS02260	BN137_RS16670
galK	galactokinase (-1-phosphate forming)	BN137_RS01525
galT	UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase	BN137_RS01520
galE	UDP-glucose 4-epimerase	BN137_RS01515	BN137_RS03010
pgmA	alpha-phosphoglucomutase	BN137_RS06550	BN137_RS09430
glk	glucokinase	BN137_RS14745	BN137_RS02630
Alternative steps:
aglE'	glucose ABC transporter, substrate-binding component (AglE)
aglF'	glucose ABC transporter, permease component 1 (AglF)
aglG'	glucose ABC transporter, permease component 2 (AglG)
aglK'	glucose ABC transporter, ATPase component (AglK)	BN137_RS14585	BN137_RS16140
bglF	glucose PTS, enzyme II (BCA components, BglF)	BN137_RS02915	BN137_RS01325
crr	glucose PTS, enzyme IIA	BN137_RS10310	BN137_RS12010
dgoA	2-dehydro-3-deoxy-6-phosphogalactonate aldolase	BN137_RS04830	BN137_RS04055
dgoD	D-galactonate dehydratase	BN137_RS08140	BN137_RS10885
dgoK	2-dehydro-3-deoxygalactonokinase	BN137_RS08150	BN137_RS03205
eda	2-keto-3-deoxygluconate 6-phosphate aldolase	BN137_RS04830	BN137_RS04055
edd	phosphogluconate dehydratase	BN137_RS04825	BN137_RS05280
gadh1	gluconate 2-dehydrogenase flavoprotein subunit
gadh2	gluconate 2-dehydrogenase cytochrome c subunit	BN137_RS16385
gadh3	gluconate 2-dehydrogenase subunit 3
galactonolactonase	galactonolactonase (either 1,4- or 1,5-lactone)	BN137_RS00940
galdh	D-galactose 1-dehydrogenase (forming 1,4- or 1,5-lactones)	BN137_RS07730	BN137_RS18050
gatY	D-tagatose-1,6-bisphosphate aldolase, catalytic subunit (GatY/KbaY)
gatZ	D-tagatose-1,6-bisphosphate aldolase, chaperone subunit (GatZ/KbaZ)
gdh	quinoprotein glucose dehydrogenase	BN137_RS05740	BN137_RS04255
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)	BN137_RS17300	BN137_RS10660
gnl	gluconolactonase	BN137_RS00940
gtsA	glucose ABC transporter, substrate-binding component (GtsA)
gtsB	glucose ABC transporter, permease component 1 (GtsB)
gtsC	glucose ABC transporter, permease component 2 (GtsC)	BN137_RS07340	BN137_RS16680
gtsD	glucose ABC transporter, ATPase component (GtsD)	BN137_RS07370	BN137_RS16695
kguD	2-keto-6-phosphogluconate reductase	BN137_RS02000	BN137_RS08125
kguK	2-ketogluconokinase	BN137_RS02010
kguT	2-ketogluconate transporter
klh	periplasmic 3'-ketolactose hydrolase
lacA	galactose-6-phosphate isomerase, lacA subunit
lacA'	periplasmic lactose 3-dehydrogenase, LacA subunit
lacB	galactose-6-phosphate isomerase, lacB subunit
lacB'	periplasmic lactose 3-dehydrogenase, cytochrome c component (LacB)
lacC	D-tagatose-6-phosphate kinase	BN137_RS01785	BN137_RS06470
lacC'	periplasmic lactose 3-dehydrogenase, LacC subunit
lacD	D-tagatose-1,6-bisphosphate aldolase (monomeric)
lacE	lactose ABC transporter, substrate-binding component
lacF	lactose ABC transporter, permease component 1	BN137_RS18075
lacG	lactose ABC transporter, permease component 2	BN137_RS10665
lacIIA	lactose PTS system, EIIA component	BN137_RS15595	BN137_RS03505
lacIIB	lactose PTS system, EIIB component	BN137_RS15590	BN137_RS03515
lacIIC	lactose PTS system, EIIC component	BN137_RS18105	BN137_RS03510
lacIICB	lactose PTS system, fused EIIC and EIIB components	BN137_RS06385	BN137_RS03510
lacK	lactose ABC transporter, ATPase component	BN137_RS16695	BN137_RS16140
lacL	heteromeric lactase, large subunit	BN137_RS02260
lacM	heteromeric lactase, small subunit
lacP	lactose permease LacP
lacS	lactose permease LacS
manX	glucose PTS, enzyme EIIAB	BN137_RS13775
manY	glucose PTS, enzyme EIIC	BN137_RS13780
manZ	glucose PTS, enzyme EIID	BN137_RS13785
MFS-glucose	glucose transporter, MFS superfamily	BN137_RS13235	BN137_RS02325
mglA	glucose ABC transporter, ATP-binding component (MglA)	BN137_RS06860	BN137_RS17460
mglB	glucose ABC transporter, substrate-binding component	BN137_RS06865	BN137_RS01920
mglC	glucose ABC transporter, permease component (MglC)	BN137_RS06855	BN137_RS17455
PAST-A	proton-associated sugar transporter A
pbgal	phospho-beta-galactosidase	BN137_RS06045	BN137_RS18110
ptsG	glucose PTS, enzyme IICB	BN137_RS11795	BN137_RS12010
ptsG-crr	glucose PTS, enzyme II (CBA components, PtsG)	BN137_RS12010	BN137_RS18365
SemiSWEET	Sugar transporter SemiSWEET
SSS-glucose	Sodium/glucose cotransporter
SWEET1	bidirectional sugar transporter SWEET1
tpi	triose-phosphate isomerase	BN137_RS05125	BN137_RS13275

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 24 2021. The underlying query database was built on Sep 17 2021.

Downloads

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