D-glucuronate catabolism in Klebsiella michiganensis M5al

GapMind for catabolism of small carbon sources

D-glucuronate catabolism in Klebsiella michiganensis M5al

Best path

Also see fitness data for the top candidates

Rules

Overview: Glucuronate utilization in GapMind is based on MetaCyc pathways D-glucuronate degradation II (oxidation of 5-keto-4-deoxyglucarate, link), a related pathway via 5-keto-4-deoxyglucarate aldolase (link), or degradation via fructuronate (link). GapMind also includes a variation on the oxidative pathway with a glucarolactonase, as in Pseudomonas putida. MetaCyc pathway I (via L-gulonate and xylitol, link) is not reported in prokaryotes and is not described here.

all:

glucuronate-transport, udh, gci and 5-dehydro-4-deoxyglucarate-degradation
or glucuronate-transport, udh, uxuL, gudD and 5-dehydro-4-deoxyglucarate-degradation
or glucuronate-transport, uxaC, uxuB, uxuA, kdgK and eda
Comment: In pathway II, dehydrogenase udh forms D-glucaro-1,5-lactone, which spontaneously rearranges to D-glucaro-1,4-lactone, and the cycloisomerase gci forms 5-dehydro-4-deoxy-D-glucarate. In P. putida, genetic data suggests that the lactone is hydrolyzed to D-glucarate by uxuL and the dehydratase gudD forms 5-dehydro-4-deoxy-D-glucarate. In the fructuronate pathway, an isomerase (uxaC) converts D-glucuronate to D-fructuronate, followed by oxidation to D-mannonate, dehydration to 2-dehydro-3-deoxy-D-gluconate, phosphorylation to 2-dehydro-3-deoxy-D-gluconate 6-phosphate, and an aldolase reaction to glyceraldehyde-3-phosphate and pyruvate.

5-dehydro-4-deoxyglucarate-degradation:

kdgD and dopDH
or garL, garR and garK
Comment: As part of pathway II, 5-dehydro-4-deoxyglucarate is dehydrated/decarboxylated to 2,5-dioxopentanoate (by kdgD) and oxidized to 2-oxoglutarate (by dopDH). Alternatively, 5-dehydro-4-deoxy-D-glucarate can be consumed by aldolase garL, which forms pyruvate and tartronate semialdehyde (2-hydroxy-3-oxopropionate); tartronate semialdehyde is reduced to D-glycerate and phosphorylated to enter glycolysis.

glucuronate-transport:

exuT
or dctP, dctQ and dctM
Comment: Transporters were identified using query: transporter:glucuronate:D-glucuronate:D-glucopyranuronate:CPD-14488:CPD-12521:CPD-15530

18 steps (15 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
exuT	D-glucuronate:H+ symporter ExuT	BWI76_RS24735	BWI76_RS09050
uxaC	D-glucuronate isomerase	BWI76_RS24730	BWI76_RS23645
uxuB	D-mannonate dehydrogenase	BWI76_RS05645	BWI76_RS19755
uxuA	D-mannonate dehydratase	BWI76_RS05650	BWI76_RS23640
kdgK	2-keto-3-deoxygluconate kinase	BWI76_RS26750	BWI76_RS26950
eda	2-keto-3-deoxygluconate 6-phosphate aldolase	BWI76_RS18095	BWI76_RS27940
Alternative steps:
dctM	D-glucuronate TRAP transporter, large permease component	BWI76_RS24135
dctP	D-glucuronate TRAP transporter, solute receptor component	BWI76_RS24125
dctQ	D-glucuronate TRAP transporter, small permease component
dopDH	2,5-dioxopentanonate dehydrogenase	BWI76_RS05620	BWI76_RS07615
garK	glycerate 2-kinase	BWI76_RS24820	BWI76_RS07025
garL	5-dehydro-4-deoxy-D-glucarate aldolase	BWI76_RS24830	BWI76_RS19980
garR	tartronate semialdehyde reductase	BWI76_RS24825	BWI76_RS07000
gci	D-glucaro-1,4-lactone cycloisomerase	BWI76_RS19325	BWI76_RS13570
gudD	D-glucarate dehydratase	BWI76_RS22825	BWI76_RS22830
kdgD	5-dehydro-4-deoxyglucarate dehydratase
udh	D-glucuronate dehydrogenase
uxuL	D-glucaro-1,5-lactonase UxuL or UxuF	BWI76_RS23720	BWI76_RS08665

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.

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