GapMind for catabolism of small carbon sources

 

L-isoleucine catabolism in Echinicola vietnamensis KMM 6221, DSM 17526

Best path

Bap2, bkdA, bkdB, bkdC, lpd, acdH, ech, ivdG, fadA, pccA, pccB, epi, mcm-large, mcm-small

Also see fitness data for the top candidates

Rules

Overview: Isoleucine degradation in GapMind is based on MetaCyc pathway L-isoleucine degradation I (link). The other pathways are fermentative and do not lead to carbon incorporation (link, link).

45 steps (26 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
Bap2 L-isoleucine permease Bap2
bkdA branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit Echvi_1750 Echvi_1221
bkdB branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit Echvi_3823 Echvi_1750
bkdC branched-chain alpha-ketoacid dehydrogenase, E2 component Echvi_2446 Echvi_0772
lpd branched-chain alpha-ketoacid dehydrogenase, E3 component Echvi_4609 Echvi_0770
acdH (2S)-2-methylbutanoyl-CoA dehydrogenase Echvi_1212 Echvi_1473
ech 2-methyl-3-hydroxybutyryl-CoA hydro-lyase Echvi_4069 Echvi_1069
ivdG 3-hydroxy-2-methylbutyryl-CoA dehydrogenase Echvi_4610 Echvi_1862
fadA 2-methylacetoacetyl-CoA thiolase Echvi_1071 Echvi_3705
pccA propionyl-CoA carboxylase, alpha subunit Echvi_3962 Echvi_0191
pccB propionyl-CoA carboxylase, beta subunit Echvi_0160 Echvi_0113
epi methylmalonyl-CoA epimerase Echvi_0089
mcm-large methylmalonyl-CoA mutase, large (catalytic) subunit Echvi_4683 Echvi_2441
mcm-small methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit Echvi_4683
Alternative steps:
acn (2R,3S)-2-methylcitrate dehydratase Echvi_4039
acnD 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming) Echvi_4039
bcaP L-isoleucine uptake transporter BcaP/CitA
brnQ L-isoleucine:cation symporter BrnQ/BraZ/BraB
dddA 3-hydroxypropionate dehydrogenase
hpcD 3-hydroxypropionyl-CoA dehydratase Echvi_4069 Echvi_0069
iolA malonate semialdehyde dehydrogenase (CoA-acylating) Echvi_0481
livF L-isoleucine ABC transporter, ATPase component 1 (LivF/BraG) Echvi_1333 Echvi_1022
livG L-isoleucine ABC transporter, ATPase component 2 (LivG/BraF) Echvi_1333 Echvi_1582
livH L-isoleucine ABC transporter, permease component 1 (LivH/BraD)
livJ L-isoleucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livM L-isoleucine ABC transporter, permease component 2 (LivM/BraE)
mcmA methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components Echvi_2441 Echvi_4683
natA L-isoleucine ABC transporter, ATPase component 1 (NatA) Echvi_1333 Echvi_3653
natB L-isoleucine ABC transporter, substrate-binding component NatB
natC L-isoleucine ABC transporter, permease component 1 (NatC)
natD L-isoleucine ABC transporter, permease component 2 (NatD)
natE L-isoleucine ABC transporter, ATPase component 2 (NatE) Echvi_1333 Echvi_3653
ofo branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
ofoA branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA
ofoB branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB
pccA1 propionyl-CoA carboxylase, biotin carboxyl carrier subunit Echvi_3962 Echvi_0191
pccA2 propionyl-CoA carboxylase, biotin carboxylase subunit Echvi_0275
pco propanyl-CoA oxidase Echvi_0738 Echvi_2990
prpB 2-methylisocitrate lyase
prpC 2-methylcitrate synthase Echvi_3057
prpD 2-methylcitrate dehydratase
prpF methylaconitate isomerase
vorA branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit VorA
vorB branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit VorB
vorC branched-chain alpha-ketoacid:ferredoxin oxidoreductase, gamma subunit VorC

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