GapMind for catabolism of small carbon sources

 

L-isoleucine catabolism in Klebsiella michiganensis M5al

Best path

livF, livG, livJ, livH, livM, ofo, 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 (31 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
livF L-isoleucine ABC transporter, ATPase component 1 (LivF/BraG) BWI76_RS26330 BWI76_RS07265
livG L-isoleucine ABC transporter, ATPase component 2 (LivG/BraF) BWI76_RS26335 BWI76_RS07270
livJ L-isoleucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3) BWI76_RS26365 BWI76_RS26350
livH L-isoleucine ABC transporter, permease component 1 (LivH/BraD) BWI76_RS26345 BWI76_RS07280
livM L-isoleucine ABC transporter, permease component 2 (LivM/BraE) BWI76_RS26340 BWI76_RS07275
ofo branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
acdH (2S)-2-methylbutanoyl-CoA dehydrogenase
ech 2-methyl-3-hydroxybutyryl-CoA hydro-lyase BWI76_RS01365 BWI76_RS20455
ivdG 3-hydroxy-2-methylbutyryl-CoA dehydrogenase BWI76_RS23705 BWI76_RS11090
fadA 2-methylacetoacetyl-CoA thiolase BWI76_RS20460 BWI76_RS01360
prpC 2-methylcitrate synthase BWI76_RS08385 BWI76_RS19140
acnD 2-methylcitrate dehydratase (2-methyl-trans-aconitate forming) BWI76_RS11940
prpF methylaconitate isomerase BWI76_RS04370 BWI76_RS14180
acn (2R,3S)-2-methylcitrate dehydratase BWI76_RS04910 BWI76_RS11940
prpB 2-methylisocitrate lyase BWI76_RS01665
Alternative steps:
Bap2 L-isoleucine permease Bap2 BWI76_RS19685 BWI76_RS07360
bcaP L-isoleucine uptake transporter BcaP/CitA
bkdA branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit BWI76_RS14160
bkdB branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit BWI76_RS14155
bkdC branched-chain alpha-ketoacid dehydrogenase, E2 component BWI76_RS04885 BWI76_RS14150
brnQ L-isoleucine:cation symporter BrnQ/BraZ/BraB BWI76_RS06240
dddA 3-hydroxypropionate dehydrogenase BWI76_RS07610
epi methylmalonyl-CoA epimerase
hpcD 3-hydroxypropionyl-CoA dehydratase BWI76_RS13115 BWI76_RS13120
iolA malonate semialdehyde dehydrogenase (CoA-acylating) BWI76_RS03070 BWI76_RS02840
lpd branched-chain alpha-ketoacid dehydrogenase, E3 component BWI76_RS04890 BWI76_RS14145
mcm-large methylmalonyl-CoA mutase, large (catalytic) subunit BWI76_RS23935
mcm-small methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit BWI76_RS23935
mcmA methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components BWI76_RS23935
natA L-isoleucine ABC transporter, ATPase component 1 (NatA) BWI76_RS26335 BWI76_RS07270
natB L-isoleucine ABC transporter, substrate-binding component NatB
natC L-isoleucine ABC transporter, permease component 1 (NatC) BWI76_RS05985
natD L-isoleucine ABC transporter, permease component 2 (NatD) BWI76_RS05990 BWI76_RS26345
natE L-isoleucine ABC transporter, ATPase component 2 (NatE) BWI76_RS26330 BWI76_RS05975
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 BWI76_RS25540 BWI76_RS13985
pccA1 propionyl-CoA carboxylase, biotin carboxyl carrier subunit BWI76_RS25540 BWI76_RS13985
pccA2 propionyl-CoA carboxylase, biotin carboxylase subunit
pccB propionyl-CoA carboxylase, beta subunit
pco propanyl-CoA oxidase
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 against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer. 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. 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