Definition of L-tryptophan biosynthesis
As rules and steps, or see full text
Rules
Overview: Tryptophan biosynthesis in GapMind is based on MetaCyc pathway L-tryptophan biosynthesis (link), from chorismate, glutamine, 5-phosphoribose-1-diphosphate, and serine.
- all: anthranilate-synthase, trpD_2, PRAI, IGPS, trpA and trpB
- anthranilate-synthase:
- trpE and trpD_1
- or trpED
- Comment: Anthranilate synthase usually has two components, as in E. coli, but single-protein systems are also known. (In E. coli, trpD is the second component fused to anthranilate phosphoribosyltransferase.)
Steps
trpE: anthranilate synthase subunit TrpE
trpD_1: glutamine amidotransferase of anthranilate synthase
- HMM TIGR00566
- Curated proteins matching anthranilate synthase component 2
- Curated proteins matching anthranilate synthase component II
- Curated proteins matching anthranilate synthase beta subunit
- UniProt sequence Q8AAD4_BACTN: SubName: Full=Anthranilate synthase component II {ECO:0000313|EMBL:AAO75638.1};
- UniProt sequence A0A1X9ZDE4_9SPHI: SubName: Full=Aminodeoxychorismate/anthranilate synthase component II {ECO:0000313|EMBL:ARS43103.1};
- UniProt sequence Q72EV2_DESVH: SubName: Full=Anthranilate synthase, glutamine amidotransferase component {ECO:0000313|EMBL:AAS94949.1}; EC=4.1.3.27 {ECO:0000313|EMBL:AAS94949.1};
- UniProt sequence B8DM46_DESVM: SubName: Full=Glutamine amidotransferase of anthranilate synthase {ECO:0000313|EMBL:ACL08690.1};
- Ignore hits to items matching EC 4.1.3.27 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.85 when looking for 'other' hits
- Comment: This component of anthranilate synthase is also known as the beta subunit or component II. Note that E. coli TrpD is this component fused to anthranilate phosphoribosyltransferase (which is described separately). Some proteins are components of both anthranilate synthase and 4-amino-4-deoxychorismate synthase (EC 2.6.1.85). Similarly, TIGR00566 also matches the amidotransferase component of para-aminobenzoate synthase. BT0531 (Q8AAD4_BACTN) and CA265_RS22895 (A0A1X9ZDE4_9SPHI) are also component II Similarly for DVU0466 (Q72EV2_DESVH) and DvMF_1745 (B8DM46_DESVM).
- Total: 1 HMMs and 16 characterized proteins
trpD_2: anthranilate phosphoribosyltransferase
- Curated proteins or TIGRFams with EC 2.4.2.18
- Ignore hits to items matching EC 4.1.3.27 when looking for 'other' hits
- Comment: Often fused to anthranilate synthase so ignore that (i.e., P00500 is labeled in BRENDA as a subunit of anthranilate synthase; it is probably anthranilate phosphoribosyltransferase as well)
- Total: 1 HMMs and 11 characterized proteins
trpED: anthranilate synthase, alpha proteobacterial clade
- HMM TIGR01815
- Ignore hits to items matching EC 4.1.3.27 when looking for 'other' hits
- Comment: Some alphaproteobacteria have a single-protein anthranilate synthase
- Total: 1 HMMs
PRAI: phosphoribosylanthranilate isomerase
- Curated proteins or TIGRFams with EC 5.3.1.24
- UniProt sequence Q8AAD7_BACTN: RecName: Full=N-(5'-phosphoribosyl)anthranilate isomerase {ECO:0000256|ARBA:ARBA00022272, ECO:0000256|HAMAP-Rule:MF_00135}; Short=PRAI {ECO:0000256|HAMAP-Rule:MF_00135}; EC=5.3.1.24 {ECO:0000256|ARBA:ARBA00012572, ECO:0000256|HAMAP-Rule:MF_00135};
- UniProt sequence A0A0H3CC53_CAUVN: RecName: Full=N-(5'-phosphoribosyl)anthranilate isomerase {ECO:0000256|ARBA:ARBA00022272, ECO:0000256|HAMAP-Rule:MF_00135}; Short=PRAI {ECO:0000256|HAMAP-Rule:MF_00135}; EC=5.3.1.24 {ECO:0000256|ARBA:ARBA00012572, ECO:0000256|HAMAP-Rule:MF_00135};
- UniProt sequence TRPF_RHIME: RecName: Full=N-(5'-phosphoribosyl)anthranilate isomerase {ECO:0000255|HAMAP-Rule:MF_00135}; Short=PRAI {ECO:0000255|HAMAP-Rule:MF_00135}; EC=5.3.1.24 {ECO:0000255|HAMAP-Rule:MF_00135};
- UniProt sequence A0A1L6JC25_9SPHN: RecName: Full=N-(5'-phosphoribosyl)anthranilate isomerase {ECO:0000256|ARBA:ARBA00022272, ECO:0000256|HAMAP-Rule:MF_00135}; Short=PRAI {ECO:0000256|HAMAP-Rule:MF_00135}; EC=5.3.1.24 {ECO:0000256|ARBA:ARBA00012572, ECO:0000256|HAMAP-Rule:MF_00135};
- Ignore hits to items matching EC 5.3.1.16 when looking for 'other' hits
- Comment: PRAI is sometimes known as trpF or as part of trpC (if fused to IGPS). In Bacteroides thetaiotaomicron, BT0528 (Q8AAD7_BACTN) has a PRAI domain (PF00697), is auxotrophic, and clusters with trp synthesis genes Similarly, annotate CCNA_03659 (A0A0H3CC53_CAUVN), SMc02767 (TRPF_RHIME), and Ga0059261_0237 (A0A1L6JC25_9SPHN). Some bacteria have a bifunctional phosphoribosylanthranilate isomerase (EC 5.3.1.24) and isomerase in histidine biosynthesis (hisA, EC 5.3.1.16), for instance P16250. (In both reactions a N-modified-1-amino-ribofuranose-5-phosphate rearranges to a linear N-modified-1-amino-ribulose-5-phosphate.) So hits to hisA are ignored.
- Total: 18 characterized proteins
IGPS: indole-3-glycerol phosphate synthase
- Curated proteins or TIGRFams with EC 4.1.1.48
- UniProt sequence E4PQZ8_MARAH: RecName: Full=Indole-3-glycerol phosphate synthase {ECO:0000256|HAMAP-Rule:MF_00134}; Short=IGPS {ECO:0000256|HAMAP-Rule:MF_00134}; EC=4.1.1.48 {ECO:0000256|HAMAP-Rule:MF_00134};
- UniProt sequence B8DM44_DESVM: RecName: Full=indole-3-glycerol-phosphate synthase {ECO:0000256|ARBA:ARBA00012362}; EC=4.1.1.48 {ECO:0000256|ARBA:ARBA00012362};
- UniProt sequence TRPC_BACTN: RecName: Full=Indole-3-glycerol phosphate synthase {ECO:0000255|HAMAP-Rule:MF_00134}; Short=IGPS {ECO:0000255|HAMAP-Rule:MF_00134}; EC=4.1.1.48 {ECO:0000255|HAMAP-Rule:MF_00134};
- UniProt sequence A0A560BXT3: RecName: Full=Indole-3-glycerol phosphate synthase {ECO:0000256|HAMAP-Rule:MF_00134}; Short=IGPS {ECO:0000256|HAMAP-Rule:MF_00134}; EC=4.1.1.48 {ECO:0000256|HAMAP-Rule:MF_00134};
- UniProt sequence A0A166NT80_PSEFL: RecName: Full=Indole-3-glycerol phosphate synthase {ECO:0000256|HAMAP-Rule:MF_00134}; Short=IGPS {ECO:0000256|HAMAP-Rule:MF_00134}; EC=4.1.1.48 {ECO:0000256|HAMAP-Rule:MF_00134};
- UniProt sequence A0A166NT80_PSEFL: RecName: Full=Indole-3-glycerol phosphate synthase {ECO:0000256|HAMAP-Rule:MF_00134}; Short=IGPS {ECO:0000256|HAMAP-Rule:MF_00134}; EC=4.1.1.48 {ECO:0000256|HAMAP-Rule:MF_00134};
- Ignore hits to items matching EC 4.1.3.27 when looking for 'other' hits
- Ignore hits to P24920 when looking for 'other' hits (phosphoribosylanthranilate isomerase (EC 5.3.1.24))
- Comment: Sometimes fused to anthranilate synthase subunits or known as trpC (if fused to PRAI). Ignore BRENDA::P24920 because annotated as phosphoribosylanthranilate isomerase but is also believed to be IGPS. And based on presence in Trp clusters and auxotrophic or cofit phenotypes, annotate somewhat diverged IGPS: HP15_3291 (E4PQZ8_MARAH), DvMF_1743 (B8DM44_DESVM), BT0529 (TRPC_BACTN), AZOBR_RS07450 (A0A560BXT3), Pf1N1B4_2549 (A0A166NT80_PSEFL), AO353_07210 (A0A0N9WG05_PSEFL).
- Total: 12 characterized proteins
trpA: indoleglycerol phosphate aldolase
- HMM TIGR00262
- Curated sequence Q9YGA9: tryptophan synthase subunit α (EC 4.1.2.8). tryptophan synthase (subunit 1/2) (EC 4.2.1.20)
- UniProt sequence A0A3N7DTH5: RecName: Full=Tryptophan synthase alpha chain {ECO:0000256|HAMAP-Rule:MF_00131}; EC=4.2.1.20 {ECO:0000256|HAMAP-Rule:MF_00131};
- UniProt sequence H0BV16: RecName: Full=Tryptophan synthase alpha chain {ECO:0000256|HAMAP-Rule:MF_00131}; EC=4.2.1.20 {ECO:0000256|HAMAP-Rule:MF_00131};
- UniProt sequence M4NLA4: RecName: Full=Tryptophan synthase alpha chain {ECO:0000256|HAMAP-Rule:MF_00131}; EC=4.2.1.20 {ECO:0000256|HAMAP-Rule:MF_00131};
- Ignore hits to items matching EC 4.2.1.20 when looking for 'other' hits
- Ignore hits to items matching EC 4.1.2.8 when looking for 'other' hits
- Comment: This reaction is 4.1.2.8 by itself or part of 4.2.1.20. The enzyme from Pyrolobus is not matched by the HMM, but is similar to the characterized trpA from Thermococcus (Q9YGA9, see PMID:11029579) APJEIK_06300 from Pedobacter sp. FW305-3-2-15-E-R2A2 (A0A3N7DTH5) can complement a trpA- strain of E. coli (Bradley Biggs). GAMENC_07330 from Acidovorax sp. FHTAMBA (H0BV16) can complement a trpA- strain of E. coli (Bradley Biggs); also it is very similar to Ac3H11_1535, which has auxotrophic phenotypes. LRK54_RS01680 from Rhodanobacter sp. FW104-10B01 (M4NLA4) can complement a trpA- strain of E. coli (Bradley Biggs); also it is similar to N515DRAFT_0116, which has auxotrophic pheonotypes.
- Total: 1 HMMs and 4 characterized proteins
trpB: tryptophan synthase
- HMM TIGR00263
- UniProt sequence P50383: RecName: Full=Tryptophan synthase beta chain 1; EC=4.2.1.20;
- Curated sequence Q97TX6: tryptophan synthase (EC 4.2.1.20)
- Ignore hits to items matching EC 4.2.1.20 when looking for 'other' hits
- Ignore hits to items matching EC 4.2.1.122 when looking for 'other' hits
- Comment: Some members of TIGR01415 might also have this activity. The family also includes indole-scavenging "trpB-2" proteins, whose presence generally indicates tryptophan synthesis (EC 4.2.1.122). The enzyme from Pyrolobus is not matched by the HMM, but is similar to the characterized trpB from Sulfolobus (P50383, see PMID:11029579) or Saccharolobus (Q97TX6) "TrpB2" proteins are reported to use phosphoserine (an intermediate in serine synthesis) rather than serine as a substrate (PMID:25184516); GapMind does not try to distinguish them from TrpB.
- Total: 1 HMMs and 2 characterized proteins
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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