GapMind for catabolism of small carbon sources

 

L-lysine catabolism in Klebsiella michiganensis M5al

Best path

argT, hisM, hisQ, hisP, cadA, patA, patD, davT, davD, gcdG, gcdH, ech, fadB, atoB

Also see fitness data for the top candidates

Rules

Overview: Lysine degradation in GapMind is based on many metacyc pathways (link), including L-lysine degradation I via cadaverine (link), pathway IV via lysine monooxygenase (link), pathway V via D-lysine (link), pathway VI via lysine 6-aminotransferase (link), pathway VIII via lysine 6-dehydrogenase (link), and fermentation to acetate and butanoate (link). Pathway X (link) is similar to pathway I (with cadaverine and glutarate as intermediates), but glutarate is consumed via glutaryl-CoA (as in pathway IV); it does not introduce any new steps. Pathways II (L-pipecolate pathway) and III (via N6-acetyllysine) and VII (via 6-amino-2-oxohexanoate) and IX (similar to pathway IV) and XI (via saccharopine) are not thought to occur in prokaryotes and are not included in GapMind.

44 steps (26 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
argT L-lysine ABC transporter, substrate-binding component ArgT BWI76_RS20340 BWI76_RS20335
hisM L-lysine ABC transporter, permease component 1 (HisM) BWI76_RS20325 BWI76_RS19230
hisQ L-lysine ABC transporter, permease component 2 (HisQ) BWI76_RS20330 BWI76_RS19235
hisP L-lysine ABC transporter, ATPase component HisP BWI76_RS20320 BWI76_RS08095
cadA lysine decarboxylase BWI76_RS07195 BWI76_RS05300
patA cadaverine aminotransferase BWI76_RS24630 BWI76_RS26375
patD 5-aminopentanal dehydrogenase BWI76_RS13425 BWI76_RS12820
davT 5-aminovalerate aminotransferase BWI76_RS26375 BWI76_RS14020
davD glutarate semialdehyde dehydrogenase BWI76_RS05620 BWI76_RS03865
gcdG succinyl-CoA:glutarate CoA-transferase
gcdH glutaryl-CoA dehydrogenase
ech (S)-3-hydroxybutanoyl-CoA hydro-lyase BWI76_RS13115 BWI76_RS20455
fadB (S)-3-hydroxybutanoyl-CoA dehydrogenase BWI76_RS01365 BWI76_RS20455
atoB acetyl-CoA C-acetyltransferase BWI76_RS23445 BWI76_RS01360
Alternative steps:
alr lysine racemase BWI76_RS00845 BWI76_RS17730
amaA L-pipecolate oxidase BWI76_RS10690
amaB L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd) BWI76_RS05620 BWI76_RS13425
amaD D-lysine oxidase
bcd butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit
bgtB L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
ctfA butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit BWI76_RS16145
ctfB butanoyl-CoA:acetoacetate CoA-transferase, beta subunit BWI76_RS16140
davA 5-aminovaleramidase BWI76_RS07990
davB L-lysine 2-monooxygenase
dpkA 1-piperideine-2-carboxylate reductase BWI76_RS07040
etfA butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit
etfB butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit
glaH glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS D-2-hydroxyglutarate synthase BWI76_RS13295
kal 3-aminobutyryl-CoA deaminase
kamA L-lysine 2,3-aminomutase BWI76_RS02410
kamD L-beta-lysine 5,6-aminomutase, alpha subunit
kamE L-beta-lysine 5,6-aminomutase, beta subunit
kce (S)-5-amino-3-oxohexanoate cleavage enzyme
kdd 3,5-diaminohexanoate dehydrogenase
lat L-lysine 6-aminotransferase BWI76_RS26375 BWI76_RS14020
lhgD L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO)
LHT L-lysine transporter
lysDH L-lysine 6-dehydrogenase
lysL L-lysine transporter LysL BWI76_RS16225
lysN 2-aminoadipate transaminase BWI76_RS10245 BWI76_RS26375
lysP L-lysine:H+ symporter LysP BWI76_RS19685 BWI76_RS06025
Slc7a1 L-lysine transporter Slc7a1
ydiJ (R)-2-hydroxyglutarate dehydrogenase BWI76_RS17050

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