GapMind for catabolism of small carbon sources

 

L-leucine catabolism in Klebsiella michiganensis M5al

Best path

livF, livG, livJ, livH, livM, ilvE, ofo, liuA, liuB, liuD, liuC, liuE, atoA, atoD, atoB

Also see fitness data for the top candidates

Rules

Overview: Leucine degradation in GapMind is based on MetaCyc pathway L-leucine degradation I, via branched alpha-keto acid dehydrogenase (link). Other pathways for are not included here because they are not linked to sequence (link) or do not result in carbon incorporation.

39 steps (25 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
livF L-leucine ABC transporter, ATPase component 1 (LivF/BraG) BWI76_RS26330 BWI76_RS07265
livG L-leucine ABC transporter, ATPase component 2 (LivG/BraF) BWI76_RS26335 BWI76_RS07270
livJ L-leucine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3) BWI76_RS26365 BWI76_RS26350
livH L-leucine ABC transporter, permease component 1 (LivH/BraD) BWI76_RS26345 BWI76_RS07280
livM L-leucine ABC transporter, permease component 2 (LivM/BraE) BWI76_RS26340 BWI76_RS07275
ilvE L-leucine transaminase BWI76_RS24235 BWI76_RS01925
ofo branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
liuA isovaleryl-CoA dehydrogenase BWI76_RS02590
liuB 3-methylcrotonyl-CoA carboxylase, alpha (biotin-containing) subunit BWI76_RS13985 BWI76_RS25540
liuD 3-methylcrotonyl-CoA carboxylase, beta subunit
liuC 3-methylglutaconyl-CoA hydratase BWI76_RS13115 BWI76_RS20455
liuE hydroxymethylglutaryl-CoA lyase
atoA acetoacetyl-CoA transferase, A subunit BWI76_RS16145
atoD acetoacetyl-CoA transferase, B subunit BWI76_RS16140
atoB acetyl-CoA C-acetyltransferase BWI76_RS23445 BWI76_RS01360
Alternative steps:
aacS acetoacetyl-CoA synthetase BWI76_RS17800 BWI76_RS23695
AAP1 L-leucine permease AAP1
aapJ ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), substrate-binding component AapJ
aapM ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 2 (AapM) BWI76_RS18355 BWI76_RS07580
aapP ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), ATPase component AapP BWI76_RS08095 BWI76_RS08965
aapQ ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 1 (AapQ)
Bap2 L-leucine permease Bap2 BWI76_RS19685 BWI76_RS07360
bcaP L-leucine uptake transporter BcaP
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-leucine:Na+ symporter BrnQ/BraB BWI76_RS06240
leuT L-leucine:Na+ symporter LeuT
lpd branched-chain alpha-ketoacid dehydrogenase, E3 component BWI76_RS04890 BWI76_RS14145
natA L-leucine ABC transporter, ATPase component 1 (NatA) BWI76_RS26335 BWI76_RS05980
natB L-leucine ABC transporter, substrate-binding component NatB
natC L-leucine ABC transporter, permease component 1 (NatC) BWI76_RS05985
natD L-leucine ABC transporter, permease component 2 (NatD) BWI76_RS05990 BWI76_RS26345
natE L-leucine 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
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