GapMind for Amino acid biosynthesis

 

L-lysine biosynthesis in Pseudomonas fluorescens FW300-N2C3

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 AO356_18775
asd aspartate semi-aldehyde dehydrogenase AO356_21420 AO356_21425
dapA 4-hydroxy-tetrahydrodipicolinate synthase AO356_04530 AO356_09275
dapB 4-hydroxy-tetrahydrodipicolinate reductase AO356_07490
dapD tetrahydrodipicolinate succinylase AO356_06070
dapC N-succinyldiaminopimelate aminotransferase AO356_06055 AO356_03470
dapE succinyl-diaminopimelate desuccinylase AO356_06090 AO356_25400
dapF diaminopimelate epimerase AO356_12735 AO356_20725
lysA diaminopimelate decarboxylase AO356_12740
Alternative steps:
dapH tetrahydrodipicolinate acetyltransferase AO356_06655
dapL N-acetyl-diaminopimelate deacetylase
DAPtransferase L,L-diaminopimelate aminotransferase AO356_05050 AO356_22880
dapX acetyl-diaminopimelate aminotransferase AO356_25355 AO356_24005
ddh meso-diaminopimelate D-dehydrogenase
hcs homocitrate synthase
hicdh homo-isocitrate dehydrogenase AO356_22135 AO356_21415
lysJ [LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase AO356_18725 AO356_17010
lysK [LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysN 2-aminoadipate:2-oxoglutarate aminotransferase AO356_16720 AO356_24005
lysT homoaconitase large subunit AO356_21400
lysU homoaconitase small subunit AO356_21405 AO356_02385
lysW 2-aminoadipate/glutamate carrier protein
lysX 2-aminoadipate-LysW ligase
lysY [LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase AO356_14490
lysZ [LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase AO356_12525

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