GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Pseudomonas fluorescens FW300-N2E2

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 (19 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase Pf6N2E2_5676
asd aspartate semi-aldehyde dehydrogenase Pf6N2E2_67 Pf6N2E2_68
dapA 4-hydroxy-tetrahydrodipicolinate synthase Pf6N2E2_2747 Pf6N2E2_3203
dapB 4-hydroxy-tetrahydrodipicolinate reductase Pf6N2E2_3366
dapD tetrahydrodipicolinate succinylase Pf6N2E2_3078
dapC N-succinyldiaminopimelate aminotransferase Pf6N2E2_3073 Pf6N2E2_2521
dapE succinyl-diaminopimelate desuccinylase Pf6N2E2_3083 Pf6N2E2_1185
dapF diaminopimelate epimerase Pf6N2E2_4418 Pf6N2E2_6030
lysA diaminopimelate decarboxylase Pf6N2E2_4419
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase Pf6N2E2_3191 Pf6N2E2_5438
dapL N-acetyl-diaminopimelate deacetylase
DAPtransferase L,L-diaminopimelate aminotransferase Pf6N2E2_2862 Pf6N2E2_3073
dapX acetyl-diaminopimelate aminotransferase Pf6N2E2_1496 Pf6N2E2_462
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase
hicdh homo-isocitrate dehydrogenase Pf6N2E2_289 Pf6N2E2_66
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase Pf6N2E2_5326 Pf6N2E2_5665
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase Pf6N2E2_5269 Pf6N2E2_1496
lysT homoaconitase large subunit Pf6N2E2_63
lysU homoaconitase small subunit Pf6N2E2_64 Pf6N2E2_2301
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase Pf6N2E2_4836
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase Pf6N2E2_4373

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