GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Caulobacter crescentus NA1000

Best path

asp-kinase, asd, dapA, dapB, dapD, dapC, dapE, dapF, lysA

Also see fitness data for the top candidates

Rules

Overview: Lysine biosynthesis in GapMind is based on MetaCyc pathways L-lysine biosynthesis I via diaminopimelate (DAP) and succinylated intermediates (link), II with DAP and acetylated intermediates (link), III with DAP and no blocking group (link), V via 2-aminoadipate and LysW carrier protein (link), and VI with DAP aminotransferase (link). Most of these pathways involve tetrahydrodipicolinate and meso-diaminopimelate, with variations in how the amino group is introduced. Pathway V instead involves L-2-aminoadipate and LysW-attached intermediates. Lysine biosynthesis IV (link), via 2-aminoadipate and saccharopine, is only reported to occur in eukaryotes and is not described here.

25 steps (20 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase CCNA_00886
asd aspartate semi-aldehyde dehydrogenase CCNA_00253 CCNA_03599
dapA 4-hydroxy-tetrahydrodipicolinate synthase CCNA_01253
dapB 4-hydroxy-tetrahydrodipicolinate reductase CCNA_03664
dapD tetrahydrodipicolinate succinylase CCNA_00283
dapC N-succinyldiaminopimelate aminotransferase CCNA_03323 CCNA_00620
dapE succinyl-diaminopimelate desuccinylase CCNA_00277 CCNA_03746
dapF diaminopimelate epimerase CCNA_03800
lysA diaminopimelate decarboxylase CCNA_02296
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase CCNA_00283 CCNA_01990
dapL N-acetyl-diaminopimelate deacetylase CCNA_02540 CCNA_02900
DAPtransferase L,L-diaminopimelate aminotransferase CCNA_01446 CCNA_01603
dapX acetyl-diaminopimelate aminotransferase CCNA_01603
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase CCNA_01610
hicdh homo-isocitrate dehydrogenase CCNA_00193
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase CCNA_00620 CCNA_02326
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase CCNA_01603 CCNA_02244
lysT homoaconitase large subunit CCNA_00196
lysU homoaconitase small subunit CCNA_00195 CCNA_03781
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase CCNA_00285

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Aug 03 2021. The underlying query database was built on Aug 03 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 paper from 2022 on GapMind for carbon sources, or view the source code, or see changes to Amino acid biosynthesis since the publication.

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