GapMind for catabolism of small carbon sources

 

L-isoleucine catabolism in Marinobacter adhaerens HP15

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 (33 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
livF L-isoleucine ABC transporter, ATPase component 1 (LivF/BraG) HP15_3059 HP15_2703
livG L-isoleucine ABC transporter, ATPase component 2 (LivG/BraF) HP15_3058 HP15_2704
livJ L-isoleucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3) HP15_3055
livH L-isoleucine ABC transporter, permease component 1 (LivH/BraD) HP15_3056 HP15_2706
livM L-isoleucine ABC transporter, permease component 2 (LivM/BraE) HP15_3057 HP15_2705
bkdA branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit HP15_61 HP15_1634
bkdB branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit HP15_1633 HP15_63
bkdC branched-chain alpha-ketoacid dehydrogenase, E2 component HP15_1631 HP15_64
lpd branched-chain alpha-ketoacid dehydrogenase, E3 component HP15_1523 HP15_65
acdH (2S)-2-methylbutanoyl-CoA dehydrogenase HP15_907 HP15_2
ech 2-methyl-3-hydroxybutyryl-CoA hydro-lyase HP15_1512 HP15_908
ivdG 3-hydroxy-2-methylbutyryl-CoA dehydrogenase HP15_2361 HP15_1007
fadA 2-methylacetoacetyl-CoA thiolase HP15_1513 HP15_5
prpC 2-methylcitrate synthase HP15_1931 HP15_1516
acnD 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming) HP15_1930 HP15_3433
prpF methylaconitate isomerase HP15_1929
acn (2R,3S)-2-methylcitrate dehydratase HP15_1930 HP15_2203
prpB 2-methylisocitrate lyase HP15_1932
Alternative steps:
Bap2 L-isoleucine permease Bap2
bcaP L-isoleucine uptake transporter BcaP/CitA
brnQ L-isoleucine:cation symporter BrnQ/BraZ/BraB
dddA 3-hydroxypropionate dehydrogenase HP15_2656 HP15_2800
epi methylmalonyl-CoA epimerase
hpcD 3-hydroxypropionyl-CoA dehydratase HP15_12 HP15_2692
iolA malonate semialdehyde dehydrogenase (CoA-acylating) HP15_2655 HP15_906
mcm-large methylmalonyl-CoA mutase, large (catalytic) subunit
mcm-small methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit HP15_1792
mcmA methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components
natA L-isoleucine ABC transporter, ATPase component 1 (NatA) HP15_3058 HP15_2704
natB L-isoleucine ABC transporter, substrate-binding component NatB
natC L-isoleucine ABC transporter, permease component 1 (NatC) HP15_3057
natD L-isoleucine ABC transporter, permease component 2 (NatD) HP15_3056 HP15_2015
natE L-isoleucine ABC transporter, ATPase component 2 (NatE) HP15_3059 HP15_4099
ofo branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused HP15_859
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 HP15_1002 HP15_4179
pccA1 propionyl-CoA carboxylase, biotin carboxyl carrier subunit HP15_3934 HP15_3222
pccA2 propionyl-CoA carboxylase, biotin carboxylase subunit HP15_3935
pccB propionyl-CoA carboxylase, beta subunit HP15_1004 HP15_2538
pco propanyl-CoA oxidase HP15_3936 HP15_2
prpD 2-methylcitrate dehydratase HP15_1928
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