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
- Comment: Chorismate mutase is usually fused to prephenate dehydratase, which makes it difficult to find this activity when it is fused to something else. As of March 2019, the PFam does not have any characterized members with other functions
- Total: 12 HMMs and 26 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
- Comment: This enzyme forms arogenate, also known as pretyrosine.
- Total: 5 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};
- UniProt sequence Q72EV4_DESVH: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:AAS94947.1}; EC=1.3.1.12 {ECO:0000313|EMBL:AAS94947.1};
- 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};
- 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).
- Total: 17 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
- 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.
- Total: 1 HMMs and 91 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};
- UniProt sequence Q72EV4_DESVH: SubName: Full=Prephenate dehydrogenase {ECO:0000313|EMBL:AAS94947.1}; EC=1.3.1.12 {ECO:0000313|EMBL:AAS94947.1};
- 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
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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