L-lysine biosynthesis in Methanothermobacter thermautotrophicus Delta H

GapMind for Amino acid biosynthesis

L-lysine biosynthesis in Methanothermobacter thermautotrophicus Delta H

Best path

asp-kinase, asd, dapA ?, dapB, DAPtransferase, dapF, lysA

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.

all:

meso-DAP and lysA
or lysW-pathway

lysW-pathway: hcs, lysT, lysU, hicdh, lysN, lysW, lysX, lysZ, lysY, lysJ and lysK

Comment: 2-oxoglutarate and acetyl-CoA are converted to homocysteine, homoaconitate and then 2-oxoadipate (by hcs-lysTU-hicdh), an aminotransferase (lysN) forms L-2-aminoadipate, lysX ligates 2-aminoadipate to lysW, lysZYJ convert LysW-aminoadipate to LysW-lysine, and lysK releases lysine.

meso-DAP:

aspartate-semialdehyde, dapA ?, dapB, dapD, dapC, dapE and dapF
or aspartate-semialdehyde, dapA ?, dapB, dapH, dapX, dapL and dapF
or aspartate-semialdehyde, dapA ?, dapB and ddh
or aspartate-semialdehyde, dapA ?, dapB, DAPtransferase and dapF
Comment: (S)-2,3,4,5-tetrahydrodipicolinate is formed from aspartate semialdehyde by dapAB. In pathway I (dapDCE), it is succinylated, transaminated, and desuccinyulated, to L,L-DAP, and then the epimerase dapF forms meso-DAP. Pathway II (dapHXL) is similar but with acetylated intermediates. In pathway III, tetrahydrodipicolinate is reductively aminated to meso-DAP in one step, by ddh. In pathway VI, an aminotransferase (DAPtransferase) forms L,L-DAP.

aspartate-semialdehyde: asp-kinase and asd

25 steps (17 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate	Class of gap
asp-kinase	aspartate kinase	MTH_RS03770
asd	aspartate semi-aldehyde dehydrogenase	MTH_RS03755
dapA ?	4-hydroxy-tetrahydrodipicolinate synthase			spurious
dapB	4-hydroxy-tetrahydrodipicolinate reductase	MTH_RS03760
DAPtransferase	L,L-diaminopimelate aminotransferase	MTH_RS00260	MTH_RS09075
dapF	diaminopimelate epimerase	MTH_RS06370
lysA	diaminopimelate decarboxylase	MTH_RS06375
Alternative steps:
dapC	N-succinyldiaminopimelate aminotransferase	MTH_RS07670	MTH_RS06385
dapD	tetrahydrodipicolinate succinylase
dapE	succinyl-diaminopimelate desuccinylase
dapH	tetrahydrodipicolinate acetyltransferase	MTH_RS07605
dapL	N-acetyl-diaminopimelate deacetylase
dapX	acetyl-diaminopimelate aminotransferase	MTH_RS09075
ddh	meso-diaminopimelate D-dehydrogenase
hcs	homocitrate synthase	MTH_RS07810	MTH_RS07070
hicdh	homo-isocitrate dehydrogenase	MTH_RS00845	MTH_RS06640
lysJ	[LysW]-2-aminoadipate semialdehyde transaminase	MTH_RS06385	MTH_RS01035
lysK	[LysW]-lysine hydrolase
lysN	2-aminoadipate:2-oxoglutarate aminotransferase	MTH_RS09075	MTH_RS06385
lysT	homoaconitase large subunit	MTH_RS07815	MTH_RS06630
lysU	homoaconitase small subunit	MTH_RS06635	MTH_RS03905
lysW	2-aminoadipate/glutamate carrier protein
lysX	2-aminoadipate-LysW ligase
lysY	[LysW]-2-aminoadipate 6-phosphate reductase	MTH_RS03985
lysZ	[LysW]-2-aminoadipate 6-kinase	MTH_RS00840

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 Apr 10 2024. The underlying query database was built on Apr 09 2024.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

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:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

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:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

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:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

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
the source code
instructions for running GapMind on your computer
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

GapMind for Amino acid biosynthesis