GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Pseudomonas fluorescens FW300-N2E3

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 (21 with candidates)

Or see definitions of steps

Step Description Best candidate 2nd candidate
asp-kinase aspartate kinase AO353_02975
asd aspartate semi-aldehyde dehydrogenase AO353_20640 AO353_20645
dapA 4-hydroxy-tetrahydrodipicolinate synthase AO353_17670 AO353_14875
dapB 4-hydroxy-tetrahydrodipicolinate reductase AO353_05640
dapD tetrahydrodipicolinate succinylase AO353_16435
dapC N-succinyldiaminopimelate aminotransferase AO353_16445 AO353_02075
dapE succinyl-diaminopimelate desuccinylase AO353_16410 AO353_29125
dapF diaminopimelate epimerase AO353_09040
lysA diaminopimelate decarboxylase AO353_09035 AO353_05445
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase AO353_04425 AO353_02015
dapL N-acetyl-diaminopimelate deacetylase AO353_28160 AO353_29020
DAPtransferase L,L-diaminopimelate aminotransferase AO353_03235 AO353_26890
dapX acetyl-diaminopimelate aminotransferase AO353_28150 AO353_26890
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase AO353_24260 AO353_15925
hicdh homo-isocitrate dehydrogenase AO353_27690 AO353_28225
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase AO353_03025 AO353_15640
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase AO353_28215 AO353_11510
lysT homoaconitase large subunit AO353_20620
lysU homoaconitase small subunit AO353_20625
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase AO353_07155
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase AO353_09240

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 preprint 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