Definition of L-tyrosine catabolism
As rules and steps, or see full text
Rules
Overview: Tyrosine utilization in GapMind is based on MetaCyc pathway tyrosine degradation I, via homogentisate (link). This pathway requires oxygen. Another pathway via 4-hydroxyphenylacetate is known (link), but the 4-hydroxyphenylpyruvate oxidase has not been linked to sequence. The other MetaCyc pathways do not yield fixed carbon or are not reported in prokaryotes.
- all: tyrosine-transport and tyrosine-degradation
- tyrosine-degradation: HPD, hmgA, maiA, fahA and acetoacetate-degradation
- Comment: In pathway I, an aminotransferase (not represented) forms 3-(4-hydroxyphenyl)pyruvate, dioxygenase HPD forms homogentisate, another oxygenase forms 4-maleyl-acetoacetate, an isomerase forms 4-fumaryl-acetoacetate, and a hydrolase yields acetoacetate and fumarate. (Fumarate is part of the TCA cycle so its catabolism is not described.)
- acetoacetate-degradation: acetoacetate-activation and atoB
- Comment: The acetoacetate is activated to acetoacetyl-CoA, and cleaved by acetyl-CoA acetyltransferase, giving two acetyl-CoA.
- acetoacetate-activation:
- atoA and atoD
- or aacS
- Comment: acetyl-CoA:acetoacetyl-CoA transferase (sometimes given EC 2.8.3.9 or EC 2.8.3.8) or succinyl-CoA:acetoacetyl-CoA transferase (EC 2.8.3.5, also known as 3-oxoacid CoA-transferase) can activate acetoacetate. These have an A and B subunit. Alternatively, an ATP-dependent ligase (aacS) can activate acetoacetate (EC 6.2.1.16).
- tyrosine-transport:
Steps
aroP: L-tyrosine transporter (AroP/FywP)
- Curated sequence F2HN33: Transporter for phenylalainine, tyrosine and tryptophan of 449 aas and 12 TMSs, FywP or YsjA
- Curated sequence P15993: Aromatic amino acid:H+ symporter, AroP of 457 aas and 12 TMSs (Cosgriff and Pittard 1997). Transports phenylalanine, tyrosine and tryptophan. aromatic amino acid:H+ symporter AroP. aromatic amino acid:H+ symporter AroP
- Curated sequence Q46065: Aromatic amino acid permease, AroP
- Curated sequence AO356_18530: L-tyrosine transporter
- Curated sequence A2RMP5: Aromatic amino acid permease FywP
- Total: 5 characterized proteins
Ac3H11_2396: L-tyrosine ABC transporter, substrate-binding component component
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Comment: A 5-part ABC transporter for tyrosine and other amino acids was identified in Acidovorax sp. GW101-3H11. It is related to branched-amino-acid transporters. The substrate-binding component (Ac3H11_2396) is not nearby but is cofit.
- Total: 1 characterized proteins
Ac3H11_1695: L-tyrosine ABC transporter, permease component 1
Ac3H11_1694: L-tyrosine ABC transporter, permease component 2
Ac3H11_1693: L-tyrosine ABC transporter, ATPase component 1
Ac3H11_1692: L-tyrosine ABC transporter, ATPase component 2
tyrP: Tyrosine permease
TAT1: L-tyrosine permease TAT1
- Curated sequence CH_091631: valine/tyrosine/tryptophan amino-acid permease. Valine/tyrosine/tryptophan amino-acid permease 1; Tyrosine and tryptophan amino acid transporter 1. Val/Tyr/Trp permease
- Total: 1 characterized proteins
MCT10: L-tyrosine transporter MCT10
- Curated sequence Q91Y77: Monocarboxylate transporter 10; MCT 10; Aromatic amino acid transporter 1; Solute carrier family 16 member 10; T-type amino acid transporter 1. The low affinity aromatic amino acid (Tyr, Trp, Phe) transporter, TAT1 (T-type amino acid transporter), MCT10, Slc16a10
- Total: 1 characterized proteins
CAT: L-tyrosine transporter CAT
tyt1: L-tyrosine:Na+ symporter Tyt1
atoA: acetoacetyl-CoA transferase, A subunit
- Curated sequence ATOD-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &alpha. ; acetyl-CoA:acetoacetyl-CoA transferase subunit α
- Curated sequence HP0691-MONOMER: Succinyl-CoA:3-ketoacid coenzyme A transferase subunit A; Succinyl-CoA:3-oxoacid CoA-transferase; OXCT A; EC 2.8.3.5. succinyl-CoA:acetoacetate CoA-transferase subunit A (EC 2.8.3.5)
- Curated sequence GFF1045: acetyl-CoA:acetoacetate CoA transferase, A subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2111: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit A
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
atoD: acetoacetyl-CoA transferase, B subunit
- Curated sequence ATOA-MONOMER: acetyl-CoA:acetoacetyl-CoA transferase subunit &beta. ; acetyl-CoA:acetoacetyl-CoA transferase subunit β
- Curated sequence HP0692-MONOMER: succinyl-CoA:acetoacetate CoA-transferase subunit B (EC 2.8.3.5)
- Curated sequence GFF1044: acetyl-CoA:acetoacetate CoA transferase, B subunit (EC 2.8.3.8)
- Curated sequence Pf6N2E2_2112: Dehydrocarnitine CoA-transferase and acetoacetate CoA-transferase, subunit B
- Ignore hits to items matching 2.8.3.5 when looking for 'other' hits
- Total: 4 characterized proteins
aacS: acetoacetyl-CoA synthetase
atoB: acetyl-CoA C-acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.9
- Ignore hits to items matching 2.3.1.16 when looking for 'other' hits
- Ignore hits to P07256 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (EC 2.3.1.9). Cytochrome b-c1 complex subunit 1, mitochondrial; Complex III subunit 1; Core protein I; Ubiquinol-cytochrome c oxidoreductase core protein 1; Ubiquinol-cytochrome c reductase 44 kDa protein)
- Ignore hits to I3R3D0 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to I3RA71 when looking for 'other' hits (acetyl-CoA C-acetyltransferase (subunit 1/2) (EC 2.3.1.9))
- Ignore hits to items matching similar to acetyl-CoA acetyltransferase when looking for 'other' hits
- Comment: Produces two acetyl-CoA from acetoacetyl-CoA and CoA. EC 2.3.1.16 describes a broader range of beta-ketothiolases. This enzyme is usually homomeric, but I3R3D0 and I3RA71 are non-catalytic subunits of an enzyme from Haloferax mediterranei that also contains a "normal" catalytic subunit (I3R3D1, I3RA72). Inclusion of P07256 was an error in BRENDA. And CharProtDB includes an odd annotation of the form "similar to acetyl-CoA acetyltransferase"
- Total: 36 characterized proteins
HPD: 4-hydroxyphenylpyruvate dioxygenase
- Curated proteins or TIGRFams with EC 1.13.11.27
- Ignore hits to Q8EKK9 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Ignore hits to Q9RSJ4 when looking for 'other' hits (4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27))
- Comment: Q8EKK9 and Q9RSJ4 are misannotated in BRENDA
- Total: 1 HMMs and 17 characterized proteins
hmgA: homogentisate dioxygenase
maiA: maleylacetoacetate isomerase
fahA: fumarylacetoacetate hydrolase
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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.
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