lactose catabolism in Rhizobium leguminosarum WSM1325

GapMind for catabolism of small carbon sources

lactose catabolism in Rhizobium leguminosarum WSM1325

Best path

lacE, lacF, lacG, lacK, lacZ, galdh, galactonolactonase, dgoD, dgoK, dgoA, 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 (39 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
lacE	lactose ABC transporter, substrate-binding component
lacF	lactose ABC transporter, permease component 1	RLEG_RS33205	RLEG_RS25060
lacG	lactose ABC transporter, permease component 2	RLEG_RS33210	RLEG_RS25055
lacK	lactose ABC transporter, ATPase component	RLEG_RS33215	RLEG_RS19335
lacZ	lactase (homomeric)	RLEG_RS18685	RLEG_RS30915
galdh	D-galactose 1-dehydrogenase (forming 1,4- or 1,5-lactones)	RLEG_RS05970	RLEG_RS02715
galactonolactonase	galactonolactonase (either 1,4- or 1,5-lactone)	RLEG_RS02700	RLEG_RS25640
dgoD	D-galactonate dehydratase	RLEG_RS15645	RLEG_RS18610
dgoK	2-dehydro-3-deoxygalactonokinase	RLEG_RS02710	RLEG_RS15350
dgoA	2-dehydro-3-deoxy-6-phosphogalactonate aldolase	RLEG_RS02705	RLEG_RS18250
glk	glucokinase	RLEG_RS22045	RLEG_RS25895
Alternative steps:
aglE'	glucose ABC transporter, substrate-binding component (AglE)	RLEG_RS01960
aglF'	glucose ABC transporter, permease component 1 (AglF)	RLEG_RS01965	RLEG_RS34400
aglG'	glucose ABC transporter, permease component 2 (AglG)	RLEG_RS01970	RLEG_RS11530
aglK'	glucose ABC transporter, ATPase component (AglK)	RLEG_RS01980	RLEG_RS25190
bglF	glucose PTS, enzyme II (BCA components, BglF)
crr	glucose PTS, enzyme IIA
eda	2-keto-3-deoxygluconate 6-phosphate aldolase	RLEG_RS18250	RLEG_RS02705
edd	phosphogluconate dehydratase	RLEG_RS01990	RLEG_RS07220
gadh1	gluconate 2-dehydrogenase flavoprotein subunit
gadh2	gluconate 2-dehydrogenase cytochrome c subunit	RLEG_RS32865	RLEG_RS04805
gadh3	gluconate 2-dehydrogenase subunit 3
galE	UDP-glucose 4-epimerase	RLEG_RS01290	RLEG_RS20720
galK	galactokinase (-1-phosphate forming)
galT	UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase
gatY	D-tagatose-1,6-bisphosphate aldolase, catalytic subunit (GatY/KbaY)	RLEG_RS26325
gatZ	D-tagatose-1,6-bisphosphate aldolase, chaperone subunit (GatZ/KbaZ)	RLEG_RS26550	RLEG_RS01485
gdh	quinoprotein glucose dehydrogenase	RLEG_RS04840	RLEG_RS32500
glcS	glucose ABC transporter, substrate-binding component (GlcS)
glcT	glucose ABC transporter, permease component 1 (GlcT)
glcU	glucose ABC transporter, permease component 2 (GlcU)	RLEG_RS23570	RLEG_RS01970
glcU'	Glucose uptake protein GlcU
glcV	glucose ABC transporter, ATPase component (GclV)	RLEG_RS14315	RLEG_RS01445
gnl	gluconolactonase	RLEG_RS18645	RLEG_RS23075
gtsA	glucose ABC transporter, substrate-binding component (GtsA)	RLEG_RS18705	RLEG_RS07325
gtsB	glucose ABC transporter, permease component 1 (GtsB)	RLEG_RS18700	RLEG_RS07330
gtsC	glucose ABC transporter, permease component 2 (GtsC)	RLEG_RS18695	RLEG_RS11530
gtsD	glucose ABC transporter, ATPase component (GtsD)	RLEG_RS25045	RLEG_RS31295
kguD	2-keto-6-phosphogluconate reductase	RLEG_RS16385	RLEG_RS21870
kguK	2-ketogluconokinase
kguT	2-ketogluconate transporter
klh	periplasmic 3'-ketolactose hydrolase
lacA	galactose-6-phosphate isomerase, lacA subunit	RLEG_RS26400
lacA'	periplasmic lactose 3-dehydrogenase, LacA subunit	RLEG_RS34385
lacB	galactose-6-phosphate isomerase, lacB subunit	RLEG_RS10205	RLEG_RS26400
lacB'	periplasmic lactose 3-dehydrogenase, cytochrome c component (LacB)	RLEG_RS21850	RLEG_RS12810
lacC	D-tagatose-6-phosphate kinase
lacC'	periplasmic lactose 3-dehydrogenase, LacC subunit
lacD	D-tagatose-1,6-bisphosphate aldolase (monomeric)
lacIIA	lactose PTS system, EIIA component
lacIIB	lactose PTS system, EIIB component
lacIIC	lactose PTS system, EIIC component
lacIICB	lactose PTS system, fused EIIC and EIIB components
lacL	heteromeric lactase, large subunit
lacM	heteromeric lactase, small subunit
lacP	lactose permease LacP
lacS	lactose permease LacS
lacY	lactose:proton symporter LacY
manX	glucose PTS, enzyme EIIAB
manY	glucose PTS, enzyme EIIC
manZ	glucose PTS, enzyme EIID
MFS-glucose	glucose transporter, MFS superfamily
mglA	glucose ABC transporter, ATP-binding component (MglA)	RLEG_RS15665	RLEG_RS15720
mglB	glucose ABC transporter, substrate-binding component	RLEG_RS15670	RLEG_RS15710
mglC	glucose ABC transporter, permease component (MglC)	RLEG_RS15660	RLEG_RS15715
PAST-A	proton-associated sugar transporter A
pbgal	phospho-beta-galactosidase	RLEG_RS18275
pgmA	alpha-phosphoglucomutase	RLEG_RS18035	RLEG_RS17235
ptsG	glucose PTS, enzyme IICB
ptsG-crr	glucose PTS, enzyme II (CBA components, PtsG)
SemiSWEET	Sugar transporter SemiSWEET
SSS-glucose	Sodium/glucose cotransporter
SWEET1	bidirectional sugar transporter SWEET1
tpi	triose-phosphate isomerase	RLEG_RS10035	RLEG_RS26395

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