Definition of L-tyrosine biosynthesis
As rules and steps, or see full text
Rules
Overview: Tyrosine biosynthesis in GapMind is based on MetaCyc pathways L-tyrosine biosynthesis I via 3-(4-hydroxyphenyl)pyruvate (link), pathway II via L-arogenate (link), pathway III via L-arogenate (link), or pathway IV via phenylalanine (link). Pathway II and III are identical except that different cofactors are used by L-arogenate dehydrogenase; these are not distinguished in GapMind. Pathways I and II/III both involve prephenate; in pathway I, prephenate is oxidized to hydroxyphenylpyruvate before being aminated, while in II/III, prephenate is aminated to arogenate before being oxidized to tyrosine. These alternatives are difficult to distinguish by sequence analysis. MetaCyc describes pathway IV as occuring in metazoa, but it also seems to be the main path to tyrosine in some aerobic bacteria (PMC7311316).
Steps
cmutase: chorismate mutase
- Curated proteins or TIGRFams with EC 5.4.99.5
- HMM PF01817
- Curated sequence P43902: prephenate dehydrogenase (EC 1.3.1.12)
- Curated sequence Q74NC4: prephenate dehydratase (EC 4.2.1.51)
- Curated sequence A8AAX2: prephenate dehydrogenase (NADP+) (EC 1.3.1.13)
- Comment: Chorismate mutase is usually fused to prephenate dehydratase, which makes it difficult to find this activity when it is fused to something else, so we included the entire pfam in the step's definition. The only other function for this family that we are aware of is 4-amino-4-deoxychorismate mutase, which is involved in the biosynthesis of some antibiotics. (Proteins that are similar to 4-amino-4-deoxychorismate mutases will be marked as medium-confidence in the results.) Several fusion proteins are missing this EC number in their annotations (P43902, Q74NC4, A8AAX2)
- Total: 12 HMMs and 47 characterized proteins
ptransferase: prephenate aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.79
- Curated proteins or TIGRFams with EC 2.6.1.78
- Ignore hits to items matching EC 2.6.1.5 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.27 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.57 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.1 when looking for 'other' hits
- Ignore hits to O50434 when looking for 'other' hits (Probable aminotransferase Rv1178; EC 2.6.1.-)
- Comment: This enzyme forms arogenate, also known as pretyrosine. Similarity to O50434 is ignored because it is not acutally characterized.
- Total: 9 characterized proteins
pre-dehydr: prephenate dehydrogenase
- Curated proteins or TIGRFams with EC 1.3.1.12
- Curated proteins or TIGRFams with EC 1.3.1.13
- UniProt sequence Q8A0T8_BACTN: SubName: Full=Chorismate mutase/prephenate dehydratase (TyrA) {ECO:0000313|EMBL:AAO79038.1};
- Curated sequence 209400: prephenate and/or arogenate dehydrogenase
- UniProt sequence D8IR44_HERSS: SubName: Full=Prephenate dehydrogenase protein {ECO:0000313|EMBL:ADJ65170.1}; EC=1.3.1.12 {ECO:0000313|EMBL:ADJ65170.1};
- UniProt sequence A0A1L6J750: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:PJI88995.1};
- Ignore hits to items matching EC 1.3.1.78 when looking for 'other' hits
- Ignore hits to items matching EC 1.3.1.43 when looking for 'other' hits
- Ignore hits to items matching EC 1.3.1.78 when looking for 'other' hits
- UniProt sequence D4GXG3: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:ADE03239.1}; EC=1.3.1.12 {ECO:0000313|EMBL:ADE03239.1};
- Ignore hits to P06959 when looking for 'other' hits (pyruvate dehydrogenase system (EC 1.2.1.104); prephenate dehydrogenase (EC 1.3.1.12); dihydrolipoyllysine-residue acetyltransferase (EC 2.3.1.12). pyruvate dehydrogenase, dihydrolipoyltransacetylase component E2. dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex; EC 2.3.1.12. pyruvate dehydrogenase, E2 subunit (EC 2.3.1.12). pyruvate dehydrogenase E2 subunit (EC 2.3.1.12))
- UniProt sequence Q92MG1: SubName: Full=Cyclohexadienyl dehydrogenase and ADH prephenate dehydrogenase {ECO:0000313|EMBL:CAC47240.1};
- Predicted: UniProt sequence E1QE65: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:ADK83851.1};
- Predicted: UniProt sequence A9A228: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:ABX12441.1};
- Comment: prephenate dehydrogenase and arogenate dehydrogenase are difficult to distinguish. 1.3.1.12 and 1.3.1.13 vary by NAD(P)H cofactor. BT3933 (Q8A0T8_BACTN), DVU0464 (Q72EV4_DESVH), HSERO_RS18425 (D8IR44_HERSS), and Ga0059261_2298 (A0A1L6J750) are auxotrophic and have prephenate dehydrogenase domains (PF02153), but their specificity is unclear. HVO_1312 (D4GXG3) is auxotrophic for tyrosine and is probably a prephenate dehydrogenase (PMC4300041). P06959 is misannotated in BRENDA and is ignored. Ac3H11_2575 (A0A162F6L0) has auxotrophic phenotypes but its specificity is unclear. Q92MG1 was confirmed by binding tyrosine in a crystal structure (PDB:4wji). In Desulfarculus, the enzyme is a bit diverged (E1QE65), but has conserved tyrosine binding residues and is in a conserved operon with aromatic amino acid biosynthesis genes. In Nitrosopumilus maritimus, NMAR_RS02920 (A9A228) is diverged but is in a conserved operon with chorismate synthase.
- Total: 24 characterized proteins
tyrB: tyrosine aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.5
- Curated proteins or TIGRFams with EC 2.6.1.27
- Curated proteins or TIGRFams with EC 2.6.1.57
- Curated proteins or TIGRFams with EC 2.6.1.1
- Ignore hits to items matching EC 2.6.1.79 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.78 when looking for 'other' hits
- Ignore hits to P12343 when looking for 'other' hits (Aspartate aminotransferase, cytoplasmic; cAspAT; Cysteine aminotransferase, cytoplasmic; Cysteine transaminase, cytoplasmic; cCAT; Glutamate oxaloacetate transaminase 1; Transaminase A; EC 2.6.1.1; EC 2.6.1.3)
- Ignore hits to MONOMER-15919 when looking for 'other' hits (phosphoserine aminotransferase monomer (EC 2.6.1.1; EC 2.6.1.52))
- Ignore hits to MONOMER-15918 when looking for 'other' hits (phosphoserine aminotransferase monomer (EC 2.6.1.52; EC 2.6.1.1))
- Ignore hits to H7CE71 when looking for 'other' hits (aromatic-amino-acid transaminase (EC 2.6.1.57))
- Ignore hits to A0A060PQX5 when looking for 'other' hits (branched-chain-amino-acid transaminase (EC 2.6.1.42))
- Ignore hits to Q845W8 when looking for 'other' hits (aspartate 4-decarboxylase (EC 4.1.1.12))
- Comment: The specificity of the aminotransferase is difficult to predict. Include EC 2.6.1.1 (aspartate amnotransferase) because it is reported to act on aromatic amino acids including tyrosine. P12343 is a fragment. link and link are involved in phosphoserine formation and it is not clear if they would act on an aromatic amino acid. H7CE71 appears to be misannotated in BRENDA and is ignored. A0A060PQX5 and Q845W8 are very similar to proteins with this activity, and might have this activity even though they are given other EC numbers, so similarity to them is ignored.
- Total: 1 HMMs and 119 characterized proteins
aro-dehydr: arogenate dehydrogenase
- Curated proteins or TIGRFams with EC 1.3.1.78
- Curated proteins or TIGRFams with EC 1.3.1.43
- Curated proteins or TIGRFams with EC 1.3.1.78
- UniProt sequence Q8A0T8_BACTN: SubName: Full=Chorismate mutase/prephenate dehydratase (TyrA) {ECO:0000313|EMBL:AAO79038.1};
- Curated sequence 209400: prephenate and/or arogenate dehydrogenase
- UniProt sequence D8IR44_HERSS: SubName: Full=Prephenate dehydrogenase protein {ECO:0000313|EMBL:ADJ65170.1}; EC=1.3.1.12 {ECO:0000313|EMBL:ADJ65170.1};
- UniProt sequence A0A1L6J750: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:PJI88995.1};
- Ignore hits to items matching EC 1.3.1.12 when looking for 'other' hits
- Ignore hits to items matching EC 1.3.1.13 when looking for 'other' hits
- Comment: Multiple EC numbers for varying use of NAD(P)H BT3933 and DVU0464 and HSERO_RS18425 are included but their specificity is uncertain
- Total: 9 characterized proteins
PAH: phenylalanine hydroxylase
Links
Downloads
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:
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