aroC encodes chorismate synthase (CS; EC 4.2.3.5), the enzyme that catalyzes the seventh and final step of the shikimate pathway. It converts 5-enolpyruvylshikimate-3-phosphate (EPSP) into chorismate via an anti-1,4 (trans) elimination of the C-3 phosphate and the C-6 proR hydrogen, introducing a second double bond into the ring system. The reaction requires reduced flavin mononucleotide (FMNH2) as an essential cofactor, even though the overall transformation involves no net change in redox state; like other bacterial monofunctional chorismate synthases, the enzyme relies on an external supply of reduced FMN rather than reducing FMN itself. Chorismate is the central branch-point metabolite of aromatic metabolism, serving as the common precursor for the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as for folate (via para-aminobenzoate), ubiquinone/menaquinone, and other aromatic metabolites. The protein belongs to the chorismate synthase family, assembles as a homotetramer, and acts as a soluble cytosolic enzyme of central metabolism.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0004107
chorismate synthase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Core molecular function. AroC is a chorismate synthase (EC 4.2.3.5), as established by the HAMAP rule MF_00300, conserved family membership (IPR000453, PF01264, TIGR00033), and mapping to RHEA:21020. This directly represents the gene's primary catalytic activity.
|
|
GO:0005829
cytosol
|
IEA
GO_REF:0000118 |
KEEP AS NON CORE |
Summary: Chorismate synthase catalyzes a soluble step of central aromatic metabolism and has no membrane-targeting features, consistent with a cytosolic localization. This is a reasonable IEA/TreeGrafter inference for a bacterial metabolic enzyme. Bacteria lack the GO cytosol/cytoplasm distinction relevant in eukaryotes, but the term is acceptable as-is; it is not a core functional annotation.
|
|
GO:0009073
aromatic amino acid family biosynthetic process
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Chorismate produced by AroC is the direct precursor of phenylalanine, tyrosine, and tryptophan, so AroC is correctly placed in aromatic amino acid biosynthesis. This is a valid biological-process annotation, though it is broader than the gene's most specific role (chorismate biosynthesis), and chorismate also feeds non-amino-acid pathways (folate, ubiquinone). Retained as a supporting/non-core process annotation. (Note: GOA label text "aromatic amino acid biosynthetic process" is the curated synonym; the canonical GO:0009073 label is "aromatic amino acid family biosynthetic process".)
|
|
GO:0009423
chorismate biosynthetic process
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Most specific and accurate biological-process annotation: AroC catalyzes the terminal (step 7/7) reaction of chorismate biosynthesis (UniPathway UPA00053, UER00090). This is the core process for the gene.
|
|
GO:0010181
FMN binding
|
IEA
GO_REF:0000118 |
ACCEPT |
Summary: Chorismate synthase requires and binds reduced FMN (FMNH2) as an essential cofactor for catalysis; the UniProt record annotates multiple FMN-binding residues (125-127, 237-238, 277, 292-296, 318). FMN binding is well supported and integral to the catalytic mechanism, so this is accepted as a genuine (though accessory-to-the-MF) molecular function annotation.
|
This report is retrieval-only and is generated directly from Asta results.
search_papers_by_relevance with snippet_search.The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The research target is AroC (chorismate synthase; EC 4.2.3.5) encoded by aroC and mapped (per the provided UniProt record) to ordered locus PP_1830 in Pseudomonas putida strain KT2440 (UniProt Q88LU7). The retrieved literature that mentions “aroC” in Pseudomonas metabolic engineering uses it consistently as a shikimate-pathway gene encoding chorismate synthase (e.g., included as a shikimate-pathway overexpression target in P. putida KT2440) and not as an unrelated gene, supporting correct symbol usage in this organism context (camposmagana2024combinatorialengineeringreveals pages 4-7).
Limitation: within the retrieved full texts, there is little direct primary characterization explicitly citing PP_1830/Q88LU7; therefore, organism-specific biochemical details for this exact protein are inferred from conserved AroC enzymology (family-level evidence) and P. putida KT2440 pathway-engineering studies.
Chorismate synthase (AroC; EC 4.2.3.5) catalyzes the terminal step of the shikimate pathway, converting 5-enolpyruvylshikimate-3-phosphate (EPSP) into chorismate with elimination of inorganic phosphate (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). The enzymatic transformation is described as a 1,4-trans elimination of the phosphate group from EPSP, which introduces a second double bond into the six-membered ring system to yield chorismate (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13).
Because chorismate is the key branch-point metabolite at the end of the shikimate pathway, AroC function is tightly tied to biosynthesis of aromatic amino acids and other chorismate-derived products (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13).
The canonical substrate is EPSP, and the product is chorismate + phosphate (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). Structural/biochemical work in other taxa (e.g., fungal chorismate synthase) explicitly models/binds EPSP together with FMNH2 at the active site and uses EPSP in enzyme assays, reinforcing EPSP as the functional substrate in chorismate synthases across organisms (rodriguesvendramini2019promisingnewantifungal pages 2-5).
Although the overall EPSP→chorismate conversion is an elimination with no net redox change, chorismate synthase requires reduced flavin mononucleotide (FMNH2) for catalysis (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). A 2024 authoritative review summarizes that monofunctional chorismate synthases (e.g., from E. coli and higher plants) are unable to reduce FMN themselves and therefore depend on externally supplied reduced FMN, whereas some organisms (e.g., fungi/protozoa) have bifunctional enzymes capable of reducing FMN using NADPH, changing how FMNH2 is supplied (shende2024theshikimatepathway pages 11-13).
Chorismate synthase is often tetrameric. For example, a mycobacterial chorismate synthase structure was solved with bound FMN and described as a tetramer (dimer of dimers) (nunes2020mycobacteriumtuberculosisshikimate pages 20-23). A fungal chorismate synthase was modeled as a homotetramer for docking/MD stability and ligand binding (rodriguesvendramini2019promisingnewantifungal pages 2-5). This supports a common structural theme that is relevant for conserved function.
The shikimate pathway comprises seven steps that convert central carbon precursors (classically PEP and E4P) into chorismate, which then branches into multiple essential biosynthetic routes (nunes2020mycobacteriumtuberculosisshikimate pages 3-7). The product chorismate is a central node feeding the biosynthesis of phenylalanine, tyrosine, and tryptophan, and also contributes to other pathways, such as PABA/folate-related metabolism and quinone-related metabolites in microbes (guida2024aminoacidbiosynthesis pages 1-2, nunes2020mycobacteriumtuberculosisshikimate pages 3-7).
In P. putida KT2440 specifically, multiple engineering studies rely on increasing shikimate/chorismate supply to produce aromatic chemicals, demonstrating that chorismate availability (and therefore AroC activity upstream) is a key determinant of metabolic output in this chassis (yu2016metabolicengineeringof pages 1-3, dias2023fromdegraderto pages 8-11, camposmagana2024combinatorialengineeringreveals pages 7-11).
No direct experimental localization for AroC (PP_1830/Q88LU7) was retrieved from the available texts. However, given that chorismate synthase catalyzes a soluble step of central metabolism and the retrieved mechanistic/structural literature treats it as a soluble enzyme (with defined quaternary structure and bound flavin), the most consistent working annotation is that AroC functions as a cytosolic enzyme in bacteria.
Evidence limitation: because no explicit localization measurement for this P. putida enzyme was retrieved, the cytosolic localization should be treated as a reasonable inference rather than directly demonstrated in KT2440 within the cited sources.
A 2024 Natural Product Reports review (covering 1997–2023) provides an up-to-date synthesis of shikimate pathway enzymology and highlights that chorismate synthase has been interrogated using kinetic isotope and structural biology methods, reiterating (i) the EPSP→chorismate phosphate-elimination chemistry and (ii) the essential requirement for FMNH2 (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). This is an authoritative, high-citation review source suitable for current “textbook-level” mechanistic statements.
A 2024 bioRxiv preprint used a design-of-experiments (Plackett–Burman) + linear modeling approach to tune expression of nine factors in P. putida shikimate and pABA biosynthesis, explicitly including aroC among the genes amplified from KT2440 and tested at two expression levels (camposmagana2024combinatorialengineeringreveals pages 4-7). The authors report pABA titers ranging from ~2 mg/L to ~232 mg/L across their engineering cycle, with a reported best yield of 0.024 mol/mol glucose (camposmagana2024combinatorialengineeringreveals pages 7-11). Critically for aroC functional annotation in a metabolic-engineering context, they report that high aroC expression can be unfavorable and conclude that mild aroC overexpression is preferable—consistent with aroC not necessarily being the dominant bottleneck compared with other steps like aroB (camposmagana2024combinatorialengineeringreveals pages 7-11).
A 2023 study engineered P. putida KT2440 to produce gallic acid from glycerol and reported 346.7 ± 0.004 mg/L final concentration after 72 h and an observed yield of 0.12 g gallic acid per g glycerol (dias2023fromdegraderto pages 8-11). While the work did not directly manipulate aroC, it demonstrates the importance of driving flux through the shikimate/chorismate node and highlights NADPH-related considerations for high-yield routes (dias2023fromdegraderto pages 8-11).
Pseudomonas putida KT2440 is used as a robust host for producing aromatic chemicals via chorismate-derived routes. A prominent example is production of para-hydroxybenzoic acid (PHBA) by expressing E. coli ubiC (chorismate lyase) to convert chorismate into PHBA, combined with a feedback-resistant DAHP synthase (aroG D146N) and deletion of competing chorismate-consuming/degrading pathways. This strategy achieved 1.73 g/L PHBA with a carbon yield of 18.1% (C-mol/C-mol) in fed-batch fermentation (yu2016metabolicengineeringof pages 1-3). These data show that maintaining sufficient chorismate supply (which depends upstream on AroC) is central to industrial aromatic production in KT2440.
The 2024 DoE study implies that, at least for pABA production in KT2440, aroC expression requires balance: overexpression beyond a mild level may reduce performance (camposmagana2024combinatorialengineeringreveals pages 7-11). This kind of result is useful for functional annotation because it indicates aroC is embedded in a network where enzyme overabundance can create cofactor demands (e.g., reduced FMN supply), imbalances, or metabolic burden, even if the enzyme is essential for producing chorismate.
A 2024 TB-focused review reiterates the selective-targeting rationale for shikimate pathway enzymes: the pathway is absent in humans and essential in certain pathogens such as Mycobacterium tuberculosis, and chorismate is a metabolic node for aromatic amino acids and other essential metabolites (guida2024aminoacidbiosynthesis pages 1-2). This expert framing supports the broad interpretation that enzymes upstream of chorismate (including AroC) underpin essential biosynthetic capacity in many microbes.
A 2024 Applied and Environmental Microbiology paper further validates the idea of targeting chorismate-utilizing enzymes (anthranilate synthase and aminodeoxychorismate synthase) as antibiotic targets, emphasizing desirable target features such as essentiality and lack of human homologs, and proposing that disrupting conserved protein–protein interactions could provide robust antibacterial strategies (funke2024validationofaminodeoxychorismate pages 1-2). While not about AroC directly, it illustrates the ongoing 2024 research emphasis on the chorismate node as an antimicrobial intervention point.
Primary molecular function: Chorismate synthase (AroC) catalyzes EPSP → chorismate + phosphate via 1,4-trans elimination; requires reduced FMN (FMNH2) for catalysis (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13).
Biological process context: terminal step of the shikimate pathway supplying chorismate, which serves as the precursor branch point for aromatic amino acids and other essential aromatic metabolites (guida2024aminoacidbiosynthesis pages 1-2, nunes2020mycobacteriumtuberculosisshikimate pages 3-7).
Cellular location (best-supported annotation from available evidence): likely cytosolic, but direct localization evidence for PP_1830/Q88LU7 in KT2440 was not retrieved in the available texts.
Application relevance: In P. putida KT2440, engineering of chorismate supply is central to bioproduction of aromatic products such as PHBA, pABA, and gallic acid; studies indicate that balanced expression of shikimate enzymes (including aroC) can matter for yield and titer (yu2016metabolicengineeringof pages 1-3, camposmagana2024combinatorialengineeringreveals pages 7-11, dias2023fromdegraderto pages 8-11).
| Aspect | Summary |
|---|---|
| Gene/protein identity | aroC; UniProt Q88LU7; ordered locus PP_1830; organism Pseudomonas putida strain KT2440; annotated as a chorismate synthase family protein in the user-supplied UniProt record. Direct organism-specific primary literature on PP_1830 itself appears limited, so some functional details below are inferred from conserved chorismate synthase biochemistry and family-level evidence plus P. putida pathway-engineering studies (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13, camposmagana2024combinatorialengineeringreveals pages 4-7). |
| Enzyme name / EC | Chorismate synthase; EC 4.2.3.5; terminal enzyme of the shikimate pathway in bacteria (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). |
| Reaction catalyzed | 5-enolpyruvylshikimate-3-phosphate (EPSP) → chorismate + phosphate; mechanistically described as a 1,4-trans elimination of phosphate from EPSP, creating the second double bond in the ring system of chorismate (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13, rodriguesvendramini2019promisingnewantifungal pages 2-5). |
| Required cofactor(s) | Requires reduced FMN (FMNH2) for activity even though the overall reaction is not net redox. In many bacterial/plant monofunctional enzymes, FMN is reduced externally (often by a separate flavin reductase or reduced flavin supply), whereas bifunctional enzymes in some fungi/protozoa can reduce FMN themselves with NADPH (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13). |
| Pathway role | Catalyzes the terminal step from EPSP to chorismate in the shikimate pathway. Chorismate is the major branch-point precursor for phenylalanine, tyrosine, tryptophan, and additional metabolites such as PABA/folate, ubiquinone/menaquinone-related products, and other aromatic metabolites (shende2024theshikimatepathway pages 10-11, shende2024theshikimatepathway pages 11-13, guida2024aminoacidbiosynthesis pages 1-2, nunes2020mycobacteriumtuberculosisshikimate pages 3-7). |
| Quaternary structure notes | Chorismate synthase is commonly reported as a tetramer; structural work on non-P. putida orthologs describes a homotetramer or tetrameric assembly important for ligand binding/stability (rodriguesvendramini2019promisingnewantifungal pages 2-5, nunes2020mycobacteriumtuberculosisshikimate pages 20-23). |
| Likely localization | No direct localization evidence for PP_1830/Q88LU7 was retrieved here. Given its role in central aromatic biosynthesis and lack of membrane-targeting evidence in the gathered sources, the enzyme is most reasonably treated as a cytosolic bacterial metabolic enzyme, but this point should be considered an inference rather than a directly sourced P. putida measurement. |
| P. putida application: PHBA production | In P. putida KT2440, shikimate/chorismate flux was engineered toward para-hydroxybenzoic acid (PHBA) by expressing E. coli ubiC and feedback-resistant aroG D146N, with deletions of pobA, pheA, trpE, and hexR. Best reported performance: 1.73 g/L PHBA and 18.1% C-mol/C-mol carbon yield in non-optimized fed-batch fermentation (yu2016metabolicengineeringof pages 5-6, yu2016metabolicengineeringof pages 1-3). |
| P. putida application: pABA production / aroC tuning | A 2024 combinatorial-expression study in P. putida found pABA titers spanning ~2–232 mg/L. High aroC overexpression was reported to have an unfavorable or only mildly beneficial effect; the authors concluded mild rather than maximal aroC expression was preferable, while aroB emerged as a stronger bottleneck (camposmagana2024combinatorialengineeringreveals pages 7-11, camposmagana2024combinatorialengineeringreveals pages 4-7). |
| P. putida application: gallic acid production | Engineering of shikimate-pathway flux in P. putida KT2440 for gallic acid production from glycerol achieved 346.7 ± 0.004 mg/L gallic acid and an observed yield of 0.12 g/g glycerol; this study did not specifically manipulate aroC, but it demonstrates practical importance of chorismate-pathway flux control in this host (dias2023fromdegraderto pages 8-11). |
Table: This table summarizes the verified identity, core enzymology, pathway context, and recent Pseudomonas putida engineering relevance of aroC/chorismate synthase. It is useful as a compact evidence-backed reference for the final research report.
References
(camposmagana2024combinatorialengineeringreveals pages 4-7): Marco A Campos-Magaña, Sara Moreno-Paz, Vitor AP Martins dos Santos, Luis Garcia-Morales, and Maria Suarez-Diez. Combinatorial engineering reveals shikimate pathway bottlenecks in para-aminobenzoic acid production in pseudomonas putida. bioRxiv, Jun 2024. URL: https://doi.org/10.1101/2024.06.17.599342, doi:10.1101/2024.06.17.599342. This article has 0 citations.
(shende2024theshikimatepathway pages 10-11): Vikram V. Shende, Katherine D. Bauman, and Bradley S. Moore. The shikimate pathway: gateway to metabolic diversity. Natural product reports, 41:604-648, Jan 2024. URL: https://doi.org/10.1039/d3np00037k, doi:10.1039/d3np00037k. This article has 173 citations and is from a peer-reviewed journal.
(shende2024theshikimatepathway pages 11-13): Vikram V. Shende, Katherine D. Bauman, and Bradley S. Moore. The shikimate pathway: gateway to metabolic diversity. Natural product reports, 41:604-648, Jan 2024. URL: https://doi.org/10.1039/d3np00037k, doi:10.1039/d3np00037k. This article has 173 citations and is from a peer-reviewed journal.
(rodriguesvendramini2019promisingnewantifungal pages 2-5): Franciele Abigail Vilugron Rodrigues-Vendramini, Cidnei Marschalk, Marina Toplak, Peter Macheroux, Patricia de Souza Bonfim-Mendonça, Terezinha Inez Estivalet Svidzinski, Flavio Augusto Vicente Seixas, and Erika Seki Kioshima. Promising new antifungal treatment targeting chorismate synthase from paracoccidioides brasiliensis. Antimicrobial Agents and Chemotherapy, Jan 2019. URL: https://doi.org/10.1128/aac.01097-18, doi:10.1128/aac.01097-18. This article has 30 citations and is from a highest quality peer-reviewed journal.
(nunes2020mycobacteriumtuberculosisshikimate pages 20-23): José E. S. Nunes, Mario A. Duque, Talita F. de Freitas, Luiza Galina, Luis F. S. M. Timmers, Cristiano V. Bizarro, Pablo Machado, Luiz A. Basso, and Rodrigo G. Ducati. Mycobacterium tuberculosis shikimate pathway enzymes as targets for the rational design of anti-tuberculosis drugs. Molecules, 25:1259, Mar 2020. URL: https://doi.org/10.3390/molecules25061259, doi:10.3390/molecules25061259. This article has 74 citations.
(nunes2020mycobacteriumtuberculosisshikimate pages 3-7): José E. S. Nunes, Mario A. Duque, Talita F. de Freitas, Luiza Galina, Luis F. S. M. Timmers, Cristiano V. Bizarro, Pablo Machado, Luiz A. Basso, and Rodrigo G. Ducati. Mycobacterium tuberculosis shikimate pathway enzymes as targets for the rational design of anti-tuberculosis drugs. Molecules, 25:1259, Mar 2020. URL: https://doi.org/10.3390/molecules25061259, doi:10.3390/molecules25061259. This article has 74 citations.
(guida2024aminoacidbiosynthesis pages 1-2): Michela Guida, Chiara Tammaro, Miriana Quaranta, Benedetta Salvucci, Mariangela Biava, Giovanna Poce, and Sara Consalvi. Amino acid biosynthesis inhibitors in tuberculosis drug discovery. Pharmaceutics, 16:725, May 2024. URL: https://doi.org/10.3390/pharmaceutics16060725, doi:10.3390/pharmaceutics16060725. This article has 3 citations.
(yu2016metabolicengineeringof pages 1-3): Shiqin Yu, Manuel R. Plan, Gal Winter, and Jens O. Krömer. Metabolic engineering of pseudomonas putida kt2440 for the production of para-hydroxy benzoic acid. Frontiers in Bioengineering and Biotechnology, Nov 2016. URL: https://doi.org/10.3389/fbioe.2016.00090, doi:10.3389/fbioe.2016.00090. This article has 76 citations.
(dias2023fromdegraderto pages 8-11): Felipe M. S. Dias, Raoní K. Pantoja, José Gregório C. Gomez, and Luiziana F. Silva. From degrader to producer: reversing the gallic acid metabolism of pseudomonas putida kt2440. International Microbiology, 26:243-255, Nov 2023. URL: https://doi.org/10.1007/s10123-022-00282-5, doi:10.1007/s10123-022-00282-5. This article has 7 citations and is from a peer-reviewed journal.
(camposmagana2024combinatorialengineeringreveals pages 7-11): Marco A Campos-Magaña, Sara Moreno-Paz, Vitor AP Martins dos Santos, Luis Garcia-Morales, and Maria Suarez-Diez. Combinatorial engineering reveals shikimate pathway bottlenecks in para-aminobenzoic acid production in pseudomonas putida. bioRxiv, Jun 2024. URL: https://doi.org/10.1101/2024.06.17.599342, doi:10.1101/2024.06.17.599342. This article has 0 citations.
(funke2024validationofaminodeoxychorismate pages 1-2): Franziska Jasmin Funke, Sandra Schlee, and Reinhard Sterner. Validation of aminodeoxychorismate synthase and anthranilate synthase as novel targets for bispecific antibiotics inhibiting conserved protein-protein interactions. Applied and Environmental Microbiology, May 2024. URL: https://doi.org/10.1128/aem.00572-24, doi:10.1128/aem.00572-24. This article has 5 citations and is from a peer-reviewed journal.
(riossoto2024inhibitionofshikimate pages 1-2): Lluvia Rios-Soto, Alicia Hernández-Campos, David Tovar-Escobar, Rafael Castillo, Erick Sierra-Campos, Mónica Valdez-Solana, Alfredo Téllez-Valencia, and Claudia Avitia-Domínguez. Inhibition of shikimate kinase from methicillin-resistant staphylococcus aureus by benzimidazole derivatives. kinetic, computational, toxicological, and biological activity studies. International Journal of Molecular Sciences, 25:5077, May 2024. URL: https://doi.org/10.3390/ijms25105077, doi:10.3390/ijms25105077. This article has 8 citations.
(yu2016metabolicengineeringof pages 5-6): Shiqin Yu, Manuel R. Plan, Gal Winter, and Jens O. Krömer. Metabolic engineering of pseudomonas putida kt2440 for the production of para-hydroxy benzoic acid. Frontiers in Bioengineering and Biotechnology, Nov 2016. URL: https://doi.org/10.3389/fbioe.2016.00090, doi:10.3389/fbioe.2016.00090. This article has 76 citations.
(guida2024aminoacidbiosynthesis pages 2-4): Michela Guida, Chiara Tammaro, Miriana Quaranta, Benedetta Salvucci, Mariangela Biava, Giovanna Poce, and Sara Consalvi. Amino acid biosynthesis inhibitors in tuberculosis drug discovery. Pharmaceutics, 16:725, May 2024. URL: https://doi.org/10.3390/pharmaceutics16060725, doi:10.3390/pharmaceutics16060725. This article has 3 citations.
id: Q88LU7
gene_symbol: aroC
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:160488
label: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
description: >-
aroC encodes chorismate synthase (CS; EC 4.2.3.5), the enzyme that catalyzes
the seventh and final step of the shikimate pathway. It converts
5-enolpyruvylshikimate-3-phosphate (EPSP) into chorismate via an anti-1,4
(trans) elimination of the C-3 phosphate and the C-6 proR hydrogen, introducing
a second double bond into the ring system. The reaction requires reduced flavin
mononucleotide (FMNH2) as an essential cofactor, even though the overall
transformation involves no net change in redox state; like other bacterial
monofunctional chorismate synthases, the enzyme relies on an external supply of
reduced FMN rather than reducing FMN itself. Chorismate is the central
branch-point metabolite of aromatic metabolism, serving as the common precursor
for the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as
for folate (via para-aminobenzoate), ubiquinone/menaquinone, and other aromatic
metabolites. The protein belongs to the chorismate synthase family, assembles as
a homotetramer, and acts as a soluble cytosolic enzyme of central metabolism.
existing_annotations:
- term:
id: GO:0004107
label: chorismate synthase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: >-
Core molecular function. AroC is a chorismate synthase (EC 4.2.3.5), as
established by the HAMAP rule MF_00300, conserved family membership
(IPR000453, PF01264, TIGR00033), and mapping to RHEA:21020. This directly
represents the gene's primary catalytic activity.
action: ACCEPT
- term:
id: GO:0005829
label: cytosol
evidence_type: IEA
original_reference_id: GO_REF:0000118
qualifier: located_in
review:
summary: >-
Chorismate synthase catalyzes a soluble step of central aromatic
metabolism and has no membrane-targeting features, consistent with a
cytosolic localization. This is a reasonable IEA/TreeGrafter inference for a
bacterial metabolic enzyme. Bacteria lack the GO cytosol/cytoplasm
distinction relevant in eukaryotes, but the term is acceptable as-is; it is
not a core functional annotation.
action: KEEP_AS_NON_CORE
- term:
id: GO:0009073
label: aromatic amino acid family biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: >-
Chorismate produced by AroC is the direct precursor of phenylalanine,
tyrosine, and tryptophan, so AroC is correctly placed in aromatic amino acid
biosynthesis. This is a valid biological-process annotation, though it is
broader than the gene's most specific role (chorismate biosynthesis), and
chorismate also feeds non-amino-acid pathways (folate, ubiquinone). Retained
as a supporting/non-core process annotation. (Note: GOA label text
"aromatic amino acid biosynthetic process" is the curated synonym; the
canonical GO:0009073 label is "aromatic amino acid family biosynthetic
process".)
action: KEEP_AS_NON_CORE
- term:
id: GO:0009423
label: chorismate biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: >-
Most specific and accurate biological-process annotation: AroC catalyzes the
terminal (step 7/7) reaction of chorismate biosynthesis (UniPathway
UPA00053, UER00090). This is the core process for the gene.
action: ACCEPT
- term:
id: GO:0010181
label: FMN binding
evidence_type: IEA
original_reference_id: GO_REF:0000118
qualifier: enables
review:
summary: >-
Chorismate synthase requires and binds reduced FMN (FMNH2) as an essential
cofactor for catalysis; the UniProt record annotates multiple FMN-binding
residues (125-127, 237-238, 277, 292-296, 318). FMN binding is well
supported and integral to the catalytic mechanism, so this is accepted as a
genuine (though accessory-to-the-MF) molecular function annotation.
action: ACCEPT
core_functions:
- description: >-
Catalyzes the terminal step of the shikimate pathway, the FMNH2-dependent
anti-1,4-elimination of phosphate from 5-enolpyruvylshikimate-3-phosphate
(EPSP) to form chorismate, supplying the branch-point precursor for aromatic
amino acid and other aromatic metabolite biosynthesis.
molecular_function:
id: GO:0004107
label: chorismate synthase activity
supported_by:
- reference_id: GO_REF:0000120
supporting_text: >-
AroC mapped to chorismate synthase (EC 4.2.3.5; RHEA:21020) by HAMAP rule
MF_00300 and conserved family membership.
- reference_id: file:PSEPK/aroC/aroC-deep-research-falcon.md
supporting_text: >-
Chorismate synthase (AroC; EC 4.2.3.5) catalyzes the terminal step of the
shikimate pathway, converting EPSP into chorismate with elimination of
phosphate via a 1,4-trans elimination, and requires reduced FMN (FMNH2) for
catalysis.
directly_involved_in:
- id: GO:0009423
label: chorismate biosynthetic process
references:
- id: GO_REF:0000118
title: TreeGrafter-generated GO annotations
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:12534463
title: >-
Complete genome sequence and comparative analysis of the metabolically
versatile Pseudomonas putida KT2440.
findings:
- statement: >-
Genome sequencing of P. putida KT2440 identified the aroC gene (PP_1830)
encoding chorismate synthase as part of the organism's metabolic gene
complement.
reference_section_type: RESULTS
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
PubMed-verified genome paper for P. putida KT2440; source of the
PP_1830/aroC gene assignment. Does not provide direct biochemical
characterization of the AroC protein.