Definition of L-phenylalanine biosynthesis
As rules and steps, or see full text
Rules
Overview: Phenylalanine biosynthesis in GapMind is based on MetaCyc pathways L-phenylalanine biosynthesis I (link), II (link), and III (link). Pathways I and III proceed via 3-phenyl-2-oxopropanoate, but with different amino acids providing the amino group for the conversion to phenylalanine. In pathway II, L-arogenate is the intermediate (the aminotransferase reaction occurs before the dehydratase reaction).
Steps
PPYAT: phenylpyruvate aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.57
- Curated proteins or TIGRFams with EC 2.6.1.1
- Curated proteins or TIGRFams with EC 2.6.1.5
- Ignore hits to P39643 when looking for 'other' hits (Transaminase BacF; Transaminase A; EC 2.6.1.-. 3-[(2S,5R)-5-hydroxy-7-oxabicyclo[4.1.0]heptan-2-yl]-2-oxopropanoate aminotransferase (EC 2.6.1.57))
- Ignore hits to H7CE71 when looking for 'other' hits (aromatic-amino-acid transaminase (EC 2.6.1.57))
- Curated sequence PHETRANTHAUERA-MONOMER: aromatic-amino-acid aminotransferase (EC 2.6.1.1)
- Curated sequence A0A060PQX5: branched-chain-amino-acid transaminase (EC 2.6.1.42)
- Ignore hits to items matching EC 2.6.1.27 when looking for 'other' hits
- Ignore hits to items matching 2.6.1.42 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-15918 when looking for 'other' hits (phosphoserine aminotransferase monomer (EC 2.6.1.52; EC 2.6.1.1))
- Ignore hits to Q93QX0 when looking for 'other' hits (Bifunctional aspartate aminotransferase and L-aspartate beta-decarboxylase; Aspartate 4-decarboxylase; ASD; AsdA; EC 2.6.1.1; EC 4.1.1.12. aspartate 4-decarboxylase (EC 4.1.1.12))
- Comment: These enzymes are usually annotated as aromatic-amino-acid transaminase, but only the activity on phenylpyruvate (to form phenylalanine) is relevant here. Phenylalanine is also considered a substrate for aspartate aminotransferases, P39643 is annotated with this EC number but is involved in bacilysin biosynthesis and probably wouldn't form phenylalanine. H7CE71 is misannotated as this in BRENDA. link has this activity but is annotated with a different EC number. A0A060PQX5 has this activity but is given a different EC number in BRENDA. link and Q93QX0 probably do not have this activity. Many branched-chain or tryptophan transaminases are also active on phenylalanine so any similarity to them is ignored. Ignore the very short protein P12343
- Total: 1 HMMs and 111 characterized proteins
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
preph-dehydratase: prephenate dehydratase
- Curated proteins or TIGRFams with EC 4.2.1.51
- UniProt sequence Q8A0T5_BACTN: RecName: Full=prephenate dehydratase {ECO:0000256|ARBA:ARBA00013147}; EC=4.2.1.51 {ECO:0000256|ARBA:ARBA00013147};
- Ignore hits to items matching EC 4.2.1.91 when looking for 'other' hits
- UniProt sequence D4GRZ0: SubName: Full=Prephenate dehydratase {ECO:0000313|EMBL:ADE02290.1}; EC=4.2.1.51 {ECO:0000313|EMBL:ADE02290.1};
- UniProt sequence A0A160HWY7: RecName: Full=prephenate dehydratase {ECO:0000256|ARBA:ARBA00013147}; EC=4.2.1.51 {ECO:0000256|ARBA:ARBA00013147};
- Predicted: UniProt sequence A0A1L8CUL6: RecName: Full=prephenate dehydratase {ECO:0000256|ARBA:ARBA00013147}; EC=4.2.1.51 {ECO:0000256|ARBA:ARBA00013147};
- Comment: prephenate dehydratase and arogenate dehydratase can be difficult to distinguish. BT3936 (Q8A0T5_BACTN) is diverged but has auxotrophic phenotypes (as do homologs Echvi_0123, CA265_RS11630). HVO_0449 (D4GRZ0) is a phenylalanine auxotroph and is probably prephenate dehydratase (PMC4300041). A0A160HWY7 from Brevundimonas is a somewhat diverged prephenate dehydratase; it has auxotrophic phenotypes. The putative prephenate dehydratase from Carboxydothermus pertinax (A0A1L8CUL6) is lacking the regulatory (ACT) domain but has the active site residues and is often encoded near aromatic amino acid synthesis genes (it might be an arogenate dehydratase instead).
- Total: 30 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
aro-dehydratase: arogenate dehydratase
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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:
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