GapMind for catabolism of small carbon sources

 

L-isoleucine catabolism in Pseudomonas fluorescens FW300-N2C3

Best path

livF, livG, livJ, livH, livM, bkdA, bkdB, bkdC, lpd, acdH, ech, ivdG, fadA, prpC, acnD, prpF, acn, prpB

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 (30 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
livF L-isoleucine ABC transporter, ATPase component 1 (LivF/BraG) AO356_05340 AO356_08480
livG L-isoleucine ABC transporter, ATPase component 2 (LivG/BraF) AO356_05335 AO356_08485
livJ L-isoleucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3) AO356_05320 AO356_08500
livH L-isoleucine ABC transporter, permease component 1 (LivH/BraD) AO356_05325 AO356_08495
livM L-isoleucine ABC transporter, permease component 2 (LivM/BraE) AO356_05330 AO356_08490
bkdA branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit AO356_22990 AO356_24880
bkdB branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit AO356_22985 AO356_24885
bkdC branched-chain alpha-ketoacid dehydrogenase, E2 component AO356_22980 AO356_08965
lpd branched-chain alpha-ketoacid dehydrogenase, E3 component AO356_22975 AO356_19705
acdH (2S)-2-methylbutanoyl-CoA dehydrogenase AO356_26355 AO356_26365
ech 2-methyl-3-hydroxybutyryl-CoA hydro-lyase AO356_02330 AO356_26360
ivdG 3-hydroxy-2-methylbutyryl-CoA dehydrogenase AO356_26345 AO356_18385
fadA 2-methylacetoacetyl-CoA thiolase AO356_02325 AO356_21640
prpC 2-methylcitrate synthase AO356_20870 AO356_19670
acnD 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming) AO356_20875 AO356_02385
prpF methylaconitate isomerase AO356_20880 AO356_28890
acn (2R,3S)-2-methylcitrate dehydratase AO356_20875 AO356_24390
prpB 2-methylisocitrate lyase AO356_20865 AO356_22080
Alternative steps:
Bap2 L-isoleucine permease Bap2 AO356_17670 AO356_28340
bcaP L-isoleucine uptake transporter BcaP/CitA
brnQ L-isoleucine:cation symporter BrnQ/BraZ/BraB AO356_19720
dddA 3-hydroxypropionate dehydrogenase AO356_21730 AO356_30225
epi methylmalonyl-CoA epimerase
hpcD 3-hydroxypropionyl-CoA dehydratase AO356_26360 AO356_30355
iolA malonate semialdehyde dehydrogenase (CoA-acylating) AO356_23175 AO356_07950
mcm-large methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit
mcmA methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
natA L-isoleucine ABC transporter, ATPase component 1 (NatA) AO356_05335 AO356_29020
natB L-isoleucine ABC transporter, substrate-binding component NatB
natC L-isoleucine ABC transporter, permease component 1 (NatC) AO356_05330
natD L-isoleucine ABC transporter, permease component 2 (NatD)
natE L-isoleucine ABC transporter, ATPase component 2 (NatE) AO356_05340 AO356_08480
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
pccA propionyl-CoA carboxylase, alpha subunit AO356_01595 AO356_02930
pccA1 propionyl-CoA carboxylase, biotin carboxyl carrier subunit AO356_12020 AO356_08195
pccA2 propionyl-CoA carboxylase, biotin carboxylase subunit
pccB propionyl-CoA carboxylase, beta subunit AO356_01585 AO356_02920
pco propanyl-CoA oxidase AO356_10850 AO356_26355
prpD 2-methylcitrate dehydratase
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