GapMind for catabolism of small carbon sources

 

L-lysine catabolism in Cupriavidus basilensis 4G11

Best path

lysP, 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 (30 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
lysP L-lysine:H+ symporter LysP RR42_RS11100 RR42_RS28305
cadA lysine decarboxylase RR42_RS15940 RR42_RS05385
patA cadaverine aminotransferase RR42_RS26850 RR42_RS26160
patD 5-aminopentanal dehydrogenase RR42_RS27780 RR42_RS26255
davT 5-aminovalerate aminotransferase RR42_RS26160 RR42_RS26240
davD glutarate semialdehyde dehydrogenase RR42_RS21760 RR42_RS24555
gcdG succinyl-CoA:glutarate CoA-transferase RR42_RS15155 RR42_RS36540
gcdH glutaryl-CoA dehydrogenase RR42_RS15400 RR42_RS28565
ech (S)-3-hydroxybutanoyl-CoA hydro-lyase RR42_RS18250 RR42_RS23710
fadB (S)-3-hydroxybutanoyl-CoA dehydrogenase RR42_RS02510 RR42_RS36415
atoB acetyl-CoA C-acetyltransferase RR42_RS07610 RR42_RS25455
Alternative steps:
alr lysine racemase
amaA L-pipecolate oxidase RR42_RS34300 RR42_RS07820
amaB L-2-aminoadipate semialdehyde dehydrogenase (AmaB/Pcd) RR42_RS18500 RR42_RS26155
amaD D-lysine oxidase
argT L-lysine ABC transporter, substrate-binding component ArgT RR42_RS29645 RR42_RS34315
bcd butanoyl-CoA dehydrogenase (NAD+, ferredoxin), dehydrogenase subunit RR42_RS00895 RR42_RS28565
bgtB L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)
ctfA butanoyl-CoA:acetoacetate CoA-transferase, alpha subunit RR42_RS06555 RR42_RS10005
ctfB butanoyl-CoA:acetoacetate CoA-transferase, beta subunit RR42_RS06560 RR42_RS35920
davA 5-aminovaleramidase RR42_RS26020
davB L-lysine 2-monooxygenase
dpkA 1-piperideine-2-carboxylate reductase RR42_RS02230 RR42_RS20320
etfA butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfA subunit RR42_RS04575
etfB butanoyl-CoA dehydrogenase (NAD+, ferredoxin), etfB subunit
glaH glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD)
hglS D-2-hydroxyglutarate synthase
hisM L-lysine ABC transporter, permease component 1 (HisM) RR42_RS29655 RR42_RS31740
hisP L-lysine ABC transporter, ATPase component HisP RR42_RS29660 RR42_RS16370
hisQ L-lysine ABC transporter, permease component 2 (HisQ) RR42_RS29650 RR42_RS04400
kal 3-aminobutyryl-CoA deaminase
kamA L-lysine 2,3-aminomutase
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 RR42_RS23480 RR42_RS32490
kdd 3,5-diaminohexanoate dehydrogenase
lat L-lysine 6-aminotransferase RR42_RS26240 RR42_RS21370
lhgD L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO) RR42_RS06495
LHT L-lysine transporter
lysDH L-lysine 6-dehydrogenase RR42_RS18505
lysL L-lysine transporter LysL
lysN 2-aminoadipate transaminase RR42_RS35305 RR42_RS21370
Slc7a1 L-lysine transporter Slc7a1 RR42_RS01585
ydiJ (R)-2-hydroxyglutarate dehydrogenase RR42_RS26635 RR42_RS06435

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