Definition of D-mannose catabolism

GapMind for catabolism of small carbon sources

Definition of D-mannose catabolism

# Mannose utilization in GapMind is based on MetaCyc pathways
# D-mannose degradation I via a PTS system (metacyc:MANNCAT-PWY),
# pathway II via mannose kinase (metacyc:PWY3O-1743),
# or conversion to fructose by mannose isomerase.

# PTS systems

# E. coli has manXYZ, where manX has EII-AB, manY has EII-C, and manZ has EII-D.
#   (ManZ is listed twice with slightly different sequence lengths).
# Similar systems are known in Lactococcus lactis, Listeria monocytogenes, and Streptococcus thermophilus.
# However, the S. thermophilus system seems not to be active due to a defective IIC domain (PMID:12957931), so
#   those proteins are marked ignore.
# L. monocytogenes also has a PTS-like regulatory system, mpoABCD, which is not included.
#   (It is reported to act as a glucose transporter, but slowly; not clear if it transports mannose.)
# There's also a paper about manLMN from Streptococcus salivarius, but I don't think it is actually
# characterized, so ignore.
# Closely related to some systems with unclear specificity, ignore those.
manX	mannose PTS system, EII-AB component ManX/ManL	curated:CharProtDB::CH_088329	curated:TCDB::D2BKY7	curated:TCDB::E1UCI0	ignore:TCDB::Q5M5W6	ignore:BRENDA::Q9S4L5	ignore:TCDB::Q04GK1	ignore:TCDB::Q2QKM4
manY	mannose PTS system, EII-C component ManY/ManM	curated:CharProtDB::CH_088330	curated:TCDB::D2BKY8	curated:TCDB::E1UCI1	ignore:TCDB::Q5M5W7	ignore:TCDB::Q8Y8W0	ignore:TCDB::Q04GK0	ignore:TCDB::Q2QKM3
manZ	mannose PTS system, EII-D component ManZ/ManN	curated:SwissProt::P69805	curated:TCDB::D2BKY9	curated:TCDB::E1UCI2	curated:TCDB::P69805	ignore:TCDB::Q5M5W8	ignore:TCDB::Q04GJ9	ignore:TCDB::Q2QKM2	ignore:BRENDA::Q5IRC0	ignore:TCDB::Q8Y8W1

# PTS systems form D-mannose 6-phosphate
mannose-PTS: manX manY manZ

# B. subtilis has a combined EII-BCA PTS system
manP	mannose PTS system, EII-CBA components	curated:BRENDA::O31645
mannose-PTS: manP

# ABC transporters are described in Saccharolobus solfataricus (formerly Sulfolobus),
# Thermus thermophilus, Thermotoga maritima,
# and Ensifer meliloti (formerly Rhizobium or Sinorhizobium); and
# fitness data identified a system in Herbaspirillum seropedicae.

# The Saccharolobus solfataricus system (4 components)
glcS	mannose ABC transporter, substrate-binding component GlcS	curated:SwissProt::Q97UZ1
glcT	mannose ABC transporter, permease component 1 (GlcT)	curated:TCDB::Q97UZ0
glcU	mannose ABC transporter, permease component 2 (GlcU)	curated:TCDB::Q97UY9
glcV	mannose ABC transporter, ATPase component GlcV	curated:BRENDA::Q97UY8

# Transporters and PTS systems were identified using
# query: transporter:mannose:D-mannose:D-mannopyranose:CPD-13559:CPD-12601
mannose-transport: glcS glcT glcU glcV

# The Thermus thermophilus system (4 components)
TT_C0211	mannose ABC transporter, ATPase component MalK1	curated:TCDB::Q72L52
TT_C0327	mannose ABC transporter, permease component 1	curated:TCDB::Q72KX3
TT_C0326	mannose ABC transporter, permease component 2	curated:TCDB::Q72KX4
TT_C0328	mannose ABC transporter, substrate-binding component	curated:TCDB::Q72KX2
mannose-transport: TT_C0211 TT_C0327 TT_C0326 TT_C0328

# The Thermotoga maritima system (5 components)
TM1746	mannose ABC transporter, substrate-binding component	curated:TCDB::Q9X268
TM1747	mannose ABC transporter, permease component 1	curated:TCDB::Q9X269
TM1748	mannose ABC transporter, permease component 2	curated:TCDB::Q9X270
TM1749	mannose ABC transporter, ATPase component 1	curated:TCDB::Q9X271
TM1750	mannose ABC transporter, ATPase component 2	curated:TCDB::Q9X272
mannose-transport: TM1746 TM1747 TM1748 TM1749 TM1750

# The Ensifer meliloti system (3 components)
frcA	mannose ABC transporter, ATPase component FrcA	curated:SwissProt::Q9F9B0
frcB	mannose ABC transporter, substrate-binding component FrcB	curated:SwissProt::Q9F9B2
frcC	mannose ABC transporter, permease component FrcC	curated:SwissProt::Q9F9B1
mannose-transport: frcA frcB frcC

# The Herbaspirillum seropedicae system (3 components)
HSERO_RS03635	mannose ABC transporter, substrate-binding component	uniprot:D8IZC6
HSERO_RS03640	mannose ABC transporter, ATPase component	uniprot:D8IZC7
HSERO_RS03645	mannose ABC transporter, permease component	uniprot:D8IZC8
mannose-transport: HSERO_RS03635 HSERO_RS03640 HSERO_RS03645

# Homomeric transporters:

STP6	mannose:H+ symporter	curated:CharProtDB::CH_091493	curated:TCDB::Q9LT15
mannose-transport: STP6

gluP	mannose:Na+ symporter	curated:TCDB::O25788	curated:reanno::SB2B:6936374
mannose-transport: gluP

glcP	mannose:H+ symporter	curated:SwissProt::O07563

mannose-transport: glcP

MST1	mannose:H+ symporter	curated:TCDB::A0ZXK6
mannose-transport: MST1

manMFS	mannose transporter, MFS superfamily	curated:reanno::pseudo5_N2C3_1:AO356_28540
mannose-transport: manMFS

# Ignore Snf3p (TCDB::Q06222 2.A.1.1.18) which has a regulatory role


# SMc03111 (P29954) is specifically important for utilizing mannose,
# which confirms it is mannose 6-phosphate isomerase
manA	mannose-6-phosphate isomerase	EC:5.3.1.8	uniprot:P29954

# In pathway I, after uptake and phosphorlation by a PTS system, mannose-6-phosphate isomerase (manA)
# produces fructose-6-phosphate, which is a central metabolic intermediate.
all: mannose-PTS manA

# Ignore some vaguely annotated mannose or mannose-6-phosphate isomerases
man-isomerase	D-mannose isomerase	EC:5.3.1.7	ignore:reanno::pseudo3_N2E3:AO353_03400	ignore:reanno::pseudo1_N1B4:Pf1N1B4_597	ignore:reanno::pseudo5_N2C3_1:AO356_05200


# SMc03109 was annotated as mannokinase but not given this EC number.
# rokA (MONOMER-19002) and hexA (Q5GAN8) are hexose kinases, including mannose kinases (PMID:PMC545704)
mannokinase	D-mannose kinase	EC:2.7.1.7	curated:reanno::Smeli:SMc03109	curated:metacyc::MONOMER-19002	uniprot:Q5GAN8

# In pathway II, after uptake, mannose kinase is followed by isomerization to fructose 6-phosphate.
all: mannose-transport mannokinase manA

import fructose.steps:scrK # fructokinase

# Or, D-mannose isomerase yields
# fructose, which can be metabolized by fructokinase (scrK).
all: mannose-transport man-isomerase scrK

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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, 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

GapMind for catabolism of small carbon sources