Definition of chorismate biosynthesis
As rules and steps, or see full text
Rules
Overview: Chorismate is the starting point for the biosynthesis of the aromatic amino acids phenylalanine, tryptophan, and tyrosine. Chorismate biosynthesis in GapMind is based on MetaCyc pathways chorismate biosynthesis I (link), from D-erythrose-4-phosphate and phosphoenolpyruvate, or II (link), from D-glyceraldeyde-3-phosphate and L-asparatate. Both pathways are identical after they reach 3-dehydroquinate.
- all: 3-dehydroquinate, aroD, aroE, aroL, aroA and aroC
- 3-dehydroquinate:
- aroG and aroB
- or tpiA, fbp, aspartate-semialdehyde, aroA' and aroB'
- Comment: Pathway I uses aroG and aroB, while pathway II uses non-canonical activities of triose-phosphate isomerase (tpiA) and fructose-bisphosphate aldolase (fbp) to form 6-deoxy-5-ketofructose 1-phosphate. AroA' condenses this with asparate semialdehyde to 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate, and AroB' cyclizes it to 3-dehydroquinate.
- aspartate-semialdehyde: asp-kinase and asd
Steps
aroG: 3-deoxy-7-phosphoheptulonate synthase
- Curated proteins or TIGRFams with EC 2.5.1.54
- UniProt sequence L0FSZ3_ECHVK: SubName: Full=3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase {ECO:0000313|EMBL:AGA76417.1};
- Ignore hits to items matching EC 4.1.2.15 when looking for 'other' hits
- Comment: 4.1.2.15 is an obsolete EC number, but it appears in a few entries. This is also known as DAHP (3-deoxy-D-arabino-heptulosonate 7-phosphate) synthase . Add Echvi_0120 because it is diverged, is confirmed by cofitness, and is essential in other Bacteroidetes. (Echvi_0120 is a fusion with chorismate mutase.)
- Total: 3 HMMs and 18 characterized proteins
aroB: 3-dehydroquinate synthase
aroD: 3-dehydroquinate dehydratase
aroE: shikimate dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.25
- Curated proteins or TIGRFams with EC 1.1.1.282
- UniProt sequence Q8A006_BACTN: SubName: Full=Shikimate 5-dehydrogenase {ECO:0000313|EMBL:AAO79320.1};
- Comment: EC 1.1.1.282 is with NAD(P)H instead of NADPH. Manually add the B. theta gene (BT4215, Q8A006_BACTN) because it is diverged, is the only good candidate, and is essential in various Bacteroidetes
- Total: 2 HMMs and 36 characterized proteins
aroL: shikimate kinase
- Curated proteins or TIGRFams with EC 2.7.1.71
- UniProt sequence AROK_BACSU: RecName: Full=Shikimate kinase {ECO:0000255|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000255|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000255|HAMAP-Rule:MF_00109};
- UniProt sequence AROK_BACTN: RecName: Full=Shikimate kinase {ECO:0000255|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000255|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000255|HAMAP-Rule:MF_00109};
- UniProt sequence L0FT15_ECHVK: RecName: Full=Shikimate kinase {ECO:0000256|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000256|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000256|HAMAP-Rule:MF_00109};
- UniProt sequence AROK_DESVH: RecName: Full=Shikimate kinase {ECO:0000255|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000255|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000255|HAMAP-Rule:MF_00109};
- UniProt sequence AROK_CAUVN: RecName: Full=Shikimate kinase {ECO:0000255|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000255|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000255|HAMAP-Rule:MF_00109};
- UniProt sequence AROK_RHIME: RecName: Full=Shikimate kinase {ECO:0000255|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000255|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000255|HAMAP-Rule:MF_00109};
- UniProt sequence I7EWF3_PHAIB: RecName: Full=Shikimate kinase {ECO:0000256|ARBA:ARBA00012154, ECO:0000256|HAMAP-Rule:MF_00109}; Short=SK {ECO:0000256|HAMAP-Rule:MF_00109}; EC=2.7.1.71 {ECO:0000256|ARBA:ARBA00012154, ECO:0000256|HAMAP-Rule:MF_00109};
- Comment: In E. coli, AroL and AroK are isozymes. In Bacillus subtilis, this gene was known as AroI, and it was cloned by complementation (see A. Nakane et al, J. Fermentation and Bioengineering 1994, 77:312-314.) That sequence is identical to AROK_BACSU. Manually add BT3393 (AROK_BACTN) from B. thetaiotaomicron because it is diverged, is the only good candidate, and is essential in various Bacteroidetes. Similarly for Echvi_0140 (L0FT15_ECHVK) from Echinicola vietnamensis. And DVU0892 (AROK_DESVH) from D. vulgaris Hildenborough is confirmed by cofitness CCNA_03103 (AROK_CAUVN) is confirmed by cofitness and similar proteins such as SMc00695 (AROK_RHIME) and PGA1_c14090 (I7EWF3_PHAIB) are essential.
- Total: 1 HMMs and 22 characterized proteins
aroA: 3-phosphoshikimate 1-carboxyvinyltransferase
- Curated proteins or TIGRFams with EC 2.5.1.19
- UniProt sequence Q72EV5_DESVH: RecName: Full=3-phosphoshikimate 1-carboxyvinyltransferase {ECO:0000256|HAMAP-Rule:MF_00210}; EC=2.5.1.19 {ECO:0000256|HAMAP-Rule:MF_00210}; AltName: Full=5-enolpyruvylshikimate-3-phosphate synthase {ECO:0000256|HAMAP-Rule:MF_00210}; Short=EPSP synthase {ECO:0000256|HAMAP-Rule:MF_00210}; Short=EPSPS {ECO:0000256|HAMAP-Rule:MF_00210};
- Comment: Add AroA from Desulfovibrio vulgaris (DVU0463) because it is a bit diverged, is conserved essential, and clusters with aromatic amino acid biosynthesis genes
- Total: 1 HMMs and 38 characterized proteins
aroC: chorismate synthase
tpiA: D-glyceraldehyde-3-phosphate phospholyase
- Curated proteins or TIGRFams with EC 5.3.1.1
- Comment: The triose-phosphate isomerase tpiA is also thought to convert D-glyceraldehyde 3-phosphate to enolaldehyde, which spontaneously converts to methylglyoxal. (Alternatively, methylglyoxal might be formed by methylgyoxal synthase, EC 4.2.3.3?)
- Total: 1 HMMs and 46 characterized proteins
fbp: 6-deoxy-5-ketofructose 1-phosphate synthase
- Curated proteins or TIGRFams with EC 2.2.1.11
- Curated proteins or TIGRFams with EC 4.1.2.13
- Ignore hits to items matching fructose%bisphosphate aldolase when looking for 'other' hits
- Comment: 6-deoxy-5-ketofructose-1-phosphate synthase is an activity of some fructose-bisphosphate aldolases (which are usually annotated as 4.1.2.13). To find the fbp in Desulfovibrio vulgaris Hildenborough and Miyazaki F, it is necessary to match more broadly. And ignore CharProtDB items with incorrect EC.
- Total: 3 HMMs and 71 characterized proteins
asp-kinase: aspartate kinase
- Curated proteins or TIGRFams with EC 2.7.2.4
- Ignore hits to O63067 when looking for 'other' hits (homoserine dehydrogenase (EC 1.1.1.3))
- Comment: For BRENDA::O63067 -- the paper describes a monofunctional hom but the sequence of O63067 is much longer and has a close homolog of functional aspartate kinase (due to alternative splicing?)
- Total: 3 HMMs and 29 characterized proteins
asd: aspartate semi-aldehyde dehydrogenase
aroA': 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase
- Curated proteins or TIGRFams with EC 2.2.1.10
- Comment: aroA' condenses 6-deoxy-5-ketofructose 1-phosphate with L-aspartate 4-semialdehyde
- Total: 2 characterized proteins
aroB': dehydroquinate synthase II
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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:
- 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, 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