GapMind for catabolism of small carbon sources

 

lactose catabolism in Escherichia coli BW25113

Best path

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

Also see fitness data for the top candidates

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.)

74 steps (46 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
lacY lactose:proton symporter LacY b0343
lacZ lactase (homomeric) b3076 b0344
galK galactokinase (-1-phosphate forming) b0757
galT UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase b0758
galE UDP-glucose 4-epimerase b0759 b2041
pgmA alpha-phosphoglucomutase b0688 b2048
glk glucokinase b2388 b0394
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) b4032
aglK' glucose ABC transporter, ATPase component (AglK) b4035 b3450
bglF glucose PTS, enzyme II (BCA components, BglF) b3722 b2715
crr glucose PTS, enzyme IIA b2417 b0679
dgoA 2-dehydro-3-deoxy-6-phosphogalactonate aldolase b1850 b4477
dgoD D-galactonate dehydratase b4478 b4297
dgoK 2-dehydro-3-deoxygalactonokinase b3693 b3526
eda 2-keto-3-deoxygluconate 6-phosphate aldolase b1850 b4477
edd phosphogluconate dehydratase b1851 b3771
gadh1 gluconate 2-dehydrogenase flavoprotein subunit
gadh2 gluconate 2-dehydrogenase cytochrome c subunit
gadh3 gluconate 2-dehydrogenase subunit 3
galactonolactonase galactonolactonase (either 1,4- or 1,5-lactone) b3379
galdh D-galactose 1-dehydrogenase (forming 1,4- or 1,5-lactones) b2426 b2842
gatY D-tagatose-1,6-bisphosphate aldolase, catalytic subunit (GatY/KbaY) b3137 b2096
gatZ D-tagatose-1,6-bisphosphate aldolase, chaperone subunit (GatZ/KbaZ) b3132 b2095
gdh quinoprotein glucose dehydrogenase b0124 b0837
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) b0262 b4035
gnl gluconolactonase
gtsA glucose ABC transporter, substrate-binding component (GtsA)
gtsB glucose ABC transporter, permease component 1 (GtsB)
gtsC glucose ABC transporter, permease component 2 (GtsC) b1312 b4032
gtsD glucose ABC transporter, ATPase component (GtsD) b4035 b3450
kguD 2-keto-6-phosphogluconate reductase b3553 b2913
kguK 2-ketogluconokinase
kguT 2-ketogluconate transporter
klh periplasmic 3'-ketolactose hydrolase
lacA galactose-6-phosphate isomerase, lacA subunit b4090
lacA' periplasmic lactose 3-dehydrogenase, LacA subunit
lacB galactose-6-phosphate isomerase, lacB subunit b4090
lacB' periplasmic lactose 3-dehydrogenase, cytochrome c component (LacB)
lacC D-tagatose-6-phosphate kinase b3916 b1723
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 b1311
lacG lactose ABC transporter, permease component 2
lacIIA lactose PTS system, EIIA component b1736
lacIIB lactose PTS system, EIIB component b1738
lacIIC lactose PTS system, EIIC component b1737
lacIICB lactose PTS system, fused EIIC and EIIB components
lacK lactose ABC transporter, ATPase component b4035 b3450
lacL heteromeric lactase, large subunit b0344 b3076
lacM heteromeric lactase, small subunit
lacP lactose permease LacP
lacS lactose permease LacS
manX glucose PTS, enzyme EIIAB b1817
manY glucose PTS, enzyme EIIC b1818
manZ glucose PTS, enzyme EIID b1819 b3140
MFS-glucose glucose transporter, MFS superfamily b2943 b2841
mglA glucose ABC transporter, ATP-binding component (MglA) b2149 b3567
mglB glucose ABC transporter, substrate-binding component b2150 b3566
mglC glucose ABC transporter, permease component (MglC) b2148 b3750
PAST-A proton-associated sugar transporter A
pbgal phospho-beta-galactosidase b3721 b2901
ptsG glucose PTS, enzyme IICB b1101 b0679
ptsG-crr glucose PTS, enzyme II (CBA components, PtsG) b0679 b1101
SemiSWEET Sugar transporter SemiSWEET
SSS-glucose Sodium/glucose cotransporter b3679
SWEET1 bidirectional sugar transporter SWEET1
tpi triose-phosphate isomerase b3919 b2926

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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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 preprint 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