Finding step PPYAT for L-phenylalanine biosynthesis in Methanococcus aeolicus Nankai-3
5 candidates for PPYAT: phenylpyruvate aminotransferase
Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway
GapMind searches the predicted proteins for candidates by using ublast (a fast alternative to protein BLAST) to find similarities to characterized proteins or by using HMMer to find similarities to enzyme models (usually from TIGRFams). For alignments to characterized proteins (from ublast), scores of 44 bits correspond to an expectation value (E) of about 0.001.
Definition of step PPYAT
- Curated proteins or TIGRFams with EC 2.6.1.57 (search)
- Curated proteins or TIGRFams with EC 2.6.1.1 (search)
- Curated proteins or TIGRFams with EC 2.6.1.5 (search)
- 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
Or cluster all characterized PPYAT proteins
This GapMind analysis is from Jul 25 2024. The underlying query database was built on Jul 25 2024.
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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