GapMind for Amino acid biosynthesis

 

Definition of L-lysine biosynthesis

As text, or see rules and steps

# Lysine biosynthesis in GapMind is based on MetaCyc
# pathways L-lysine biosynthesis I via diaminopimelate (DAP) and
# succinylated intermediates (metacyc:DAPLYSINESYN-PWY),
# II with DAP and acetylated intermediates (metacyc:PWY-2941),
# III with DAP and no blocking group (metacyc:PWY-2942),
# V via 2-aminoadipate and LysW carrier protein (metacyc:PWY-3081),
# and VI with DAP aminotransferase (metacyc:PWY-5097).
# 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 (metacyc:LYSINE-AMINOAD-PWY), via 2-aminoadipate and saccharopine,
# is only reported to occur in eukaryotes and is not described here.

import met.steps:aspartate-semialdehyde

dapA	4-hydroxy-tetrahydrodipicolinate synthase	EC:4.3.3.7

# Formerly known as dihydrodipicolinate reductase.
# Echvi_2395 (uniprot:L0G028_ECHVK) and CA265_RS15670 (uniprot:A0A1X9Z7Q6_9SPHI) are somewhat diverged,
# but conserved essentiality confirms they are dapB.
dapB	4-hydroxy-tetrahydrodipicolinate reductase	EC:1.17.1.8	uniprot:L0G028_ECHVK	uniprot:A0A1X9Z7Q6_9SPHI

# Formerly known as 2,3,4,5-tetrahydropyridine-2-carboxylate N-succinyltransferase
dapD	tetrahydrodipicolinate succinylase	EC:2.3.1.117

# 2.6.1.52 is the EC number for 3-phosphoserine aminotransferase (serC), which catalyzes
# this reaction in E. coli
dapC	N-succinyldiaminopimelate aminotransferase	EC:2.6.1.17	EC:2.6.1.52

dapE	succinyl-diaminopimelate desuccinylase	EC:3.5.1.18

# L,L-diaminopimelate to meso-diaminopimelate
dapF	diaminopimelate epimerase	EC:5.1.1.7

lysA	diaminopimelate decarboxylase	EC:4.1.1.20

# Also known as ykuQ
dapH	tetrahydrodipicolinate acetyltransferase	EC:2.3.1.89

# Also known as patA in Bacillus subtilis
dapX	acetyl-diaminopimelate aminotransferase	term:N-acetyl-LL-diaminopimelate aminotransferase

# Also known as ykuR
dapL	N-acetyl-diaminopimelate deacetylase	EC:3.5.1.47

# In reverse, this converts tetrahydrodipicolinate to meso-DAP.
ddh	meso-diaminopimelate D-dehydrogenase	EC:1.4.1.16


# This enzyme is sometimes known as dapL. In reverse, it converts tetrahydrodipicolinate to L,L-DAP.
DAPtransferase	L,L-diaminopimelate aminotransferase	EC:2.6.1.83

# forming (2R)-homocitrate
hcs	homocitrate synthase	EC:2.3.3.14

# (2R)-homocitrate to (1R,2S)-homoisocitrate via cis-homoaconitate
lysT	homoaconitase large subunit	term:homoaconitase large subunit	ignore_other:EC 4.2.1.114	ignore_other:EC 4.2.1.36
lysU	homoaconitase small subunit	term:homoaconitase small subunit	ignore_other:EC 4.2.1.114	ignore_other:EC 4.2.1.36

# homoisocitrate to 2-oxoadipate. This rule also matches some isocitrate/homoisocitrate dehydrogenases (1.1.1.286)
# which often have multiple subunits in eukaryotes; this is not represented here.
hicdh	homo-isocitrate dehydrogenase	EC:1.1.1.87	EC:1.1.1.286

# 2-oxoadipate to 2-aminoadipate
lysN	2-aminoadipate:2-oxoglutarate aminotransferase	EC:2.6.1.39

# LysW is a carrier protein for intermediates in lysine or ornithine biosynthesis.
# TK0279 (uniprot:Q5JFV9) from Thermococcus kodakarensis was characterized, see PMC5076833.
lysW	2-aminoadipate/glutamate carrier protein	term:alpha-aminoadipate%carrier	uniprot:Q5JFV9

# TK0278 (uniprot:Q5JFW0) is described in PMC5076833.
lysX	2-aminoadipate-LysW ligase	EC:6.3.2.43	uniprot:Q5JFW0

# TK0276 (uniprot:Q5JFW2) has also been characterized (PMC5076833).
lysZ	[LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase	term:[LysW]-aminoadipate kinase	term:[LysW]-aminoadipate/[LysW]-glutamate kinase	uniprot:Q5JFW2

# TK0277 (uniprot:Q5JFW1) has also been characterized (PMC5076833).
lysY	[LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase	term:[LysW]-L-2-aminoadipate 6-phosphate reductase	term:[LysW]-L-2-aminoadipate/[LysW]-L-glutamate phosphate reductase	uniprot:Q5JFW1

# TK0275 (uniprot:Q5JFW3) has also been characterized (PMC5076833).
lysJ	[LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase	term:[LysW]-aminoadipate semialdehyde transaminase	term:[LysW]-aminoadipate semialdehyde/glutamate semialdehyde transaminase	uniprot:Q5JFW3

# TK0274 (uniprot:Q5JFW4) has also been characterized (PMC5076833).
lysK	[LysW]-lysine hydrolase / [LysW]-ornithine hydrolase	term:LysW%lysine%hydrolase	term:aminoadipate carrier protein%lysine%hydrolase	uniprot:Q5JFW4

# (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.
meso-DAP: aspartate-semialdehyde dapA dapB dapD dapC dapE dapF
meso-DAP: aspartate-semialdehyde dapA dapB dapH dapX dapL dapF
meso-DAP: aspartate-semialdehyde dapA dapB ddh
meso-DAP: aspartate-semialdehyde dapA dapB DAPtransferase dapF

# 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.
lysW-pathway: hcs lysT lysU hicdh lysN lysW lysX lysZ lysY lysJ lysK

all: meso-DAP lysA
all: lysW-pathway

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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 against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer. 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. 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