Definition of L-threonine biosynthesis
As rules and steps, or see full text
Rules
Overview: Threonine biosynthesis in GapMind is based on MetaCyc pathway L-threonine biosynthesis (link).
- all:
- homoserine: aspartate-semialdehyde and hom
- aspartate-semialdehyde: asp-kinase and asd
Steps
asp-kinase: aspartate kinase
- Curated proteins or TIGRFams with EC 2.7.2.4
- Ignore hits to O63067 when looking for 'other' hits (homoserine dehydrogenase (EC 1.1.1.3))
- Ignore hits to Q46133 when looking for 'other' hits (aspartate kinase (EC 2.7.2.4))
- Comment: For BRENDA::O63067 -- the paper describes a monofunctional hom but the sequence of O63067 is much longer and has a close homolog of functional aspartate kinase (due to alternative splicing?). In Corynebacterium, aspartate kinase has two subunits, both apparently encoded by the same gene by using start codons (PMID:1956296); Q46133 is the shorter regulatory subunit and lacks the catalytic domain, so it does not suffice for activity and is ignored.
- Total: 3 HMMs and 36 characterized proteins
asd: aspartate semi-aldehyde dehydrogenase
hom: homoserine dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.3
- UniProt sequence A0A1L6J6Q3: RecName: Full=Homoserine dehydrogenase {ECO:0000256|ARBA:ARBA00013213, ECO:0000256|RuleBase:RU000579}; EC=1.1.1.3 {ECO:0000256|ARBA:ARBA00013213, ECO:0000256|RuleBase:RU000579};
- UniProt sequence Q8A541_BACTN: SubName: Full=Aspartokinase/homoserine dehydrogenase {ECO:0000313|EMBL:AAO77510.1};
- UniProt sequence B8DRS3_DESVM: RecName: Full=Homoserine dehydrogenase {ECO:0000256|ARBA:ARBA00013213, ECO:0000256|RuleBase:RU000579}; EC=1.1.1.3 {ECO:0000256|ARBA:ARBA00013213, ECO:0000256|RuleBase:RU000579};
- UniProt sequence A0A168MV81: RecName: Full=homoserine dehydrogenase {ECO:0000256|ARBA:ARBA00013213}; EC=1.1.1.3 {ECO:0000256|ARBA:ARBA00013213};
- Comment: Ga0059261_2711 (A0A1L6J6Q3) from Sphingomonas koreensis DSMZ 15582 is distant from characterized homoserine dehydrogenases and is confirmed by fitness data. BT2403 from Bacteroides thetaiotaomicron (Q8A541_BACTN) is a fusion of aspartate kinase and homoserine dehydrogenase. The homoserine dehydrogenase portion is somewhat diverged. Its role is confirmed by strong cofitness with threonine synthase (the defined media for B. thetaiotaomicron included methionine). DvMF_1412 from Desulfovibrio vulgaris Miyazaki F (B8DRS3_DESVM) is a somewhat diverged homoserine dehydrogenase; it has auxotrophic phenotypes. A0A168MV81 from Brevundimonas is a somewhat diverged homoserine dehydrogenase (fused to aspartate kinase); it has auxotrophic phenotypes.
- Total: 33 characterized proteins
thrB: homoserine kinase
homK: putative homoserine phosphotransferase
- UniProt sequence Q8PX04: RecName: Full=2,3-bisphosphoglycerate-independent phosphoglycerate mutase; Short=BPG-independent PGAM; Short=Phosphoglyceromutase; Short=aPGAM; EC=5.4.2.12;
- Comment: BT2402 (Q8PX04) is required for threonine synthesis (PMC7311316) and belongs to a family (TIGR02535) that was proposed replace the missing homoserine kinase. This family is also known as ThrB2 (PMC9026213). Homologs from Phocaeicola are also required for threonine synthesis (Surya Tripathi, personal communication). The HomK family is often encoded next to aspartate kinase and threonine synthase. It is related to phosphoglycerate mutases and might transfer phosphate groups from a donor such as phosphoenolpyruvate to homoserine. In GapMind, HomK is described separately from ThrB because it probably carries out a different reaction.
- Total: 1 characterized proteins
thrC: threonine synthase
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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