STS3 (Stilbene synthase 3 / Resveratrol synthase 3 / Trihydroxystilbene synthase 3, EC 2.3.1.95) is a cytosolic type III polyketide synthase of the chalcone/stilbene synthase family in grapevine. It catalyzes the iterative condensation of one molecule of 4-coumaroyl-CoA (p-coumaroyl-CoA) with three molecules of malonyl-CoA, followed by an intramolecular aldol (C2->C7) cyclization and decarboxylation, to produce trans-resveratrol (3,4',5-trihydroxystilbene). Resveratrol is the major stilbenoid phytoalexin of grapevine and is antimicrobial. STS3 belongs to the unusually large grapevine STS gene family (~48 genes, >=32 functional), which arose from chalcone synthase (CHS) by convergent evolution; STS and CHS share identical substrates and a common linear tetraketide intermediate but diverge in their cyclization chemistry (STS uses aldol cyclization to form a stilbene; CHS uses Claisen cyclization to form naringenin chalcone). STS3 is the committed enzyme of stilbene/phytoalexin biosynthesis and is transcriptionally induced by biotic and abiotic stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0006952
defense response
|
IEA
GO_REF:0000043 |
MARK AS OVER ANNOTATED |
Summary: Retired SPKW (keyword2GO) annotation derived from the UniProt keyword "Plant defense" / "Stress response". STS3 is genuinely defense-associated because its product resveratrol is an antimicrobial phytoalexin, but the protein's molecular function is a biosynthetic synthase, not a defense effector or pathogen sensor. Annotating the enzyme directly to GO:0006952 "defense response" conflates the downstream protective role of the metabolite with the catalytic function of the enzyme.
Reason: GOA's removal of this annotation was JUSTIFIED. This is a textbook process-conflation / "biosynthetic-enzyme-labelled-with-the-downstream-process" over-annotation: the SPKW pipeline mapped the UniProt "Plant defense" keyword directly onto the enzyme, but STS3 does not itself sense or respond to pathogens. It biosynthesizes trans-resveratrol, a stilbene that happens to be a phytoalexin. The defense-relevant role of STS3 is properly captured by the more specific biosynthetic-process terms GO:0009811 "stilbene biosynthetic process" and GO:0052315 "phytoalexin biosynthetic process" (a child of both secondary metabolite biosynthetic process and toxin biosynthetic process), which convey the defense context without misrepresenting the enzyme as a defense response gene. GO:0006952 is too broad and is the wrong granularity for a committed biosynthetic enzyme. The flag retired:true is retained; GOA was correct to retire the SPKW keyword2GO pipeline for cellular organisms and to drop this annotation. A more accurate replacement BP annotation is suggested below as a NEW entry.
Supporting Evidence:
PMID:1898048
The mechanisms controlling the induction of stilbene synthase and phenylalanine ammonia-lyase (PAL), two putative key regulatory enzymes of the biosynthetic pathway to stilbene phytoalexins
PMID:22961129
Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene backbone
PMID:22961129
In addition to their participation in defense mechanisms in plants, stilbenes, such as resveratrol, display important pharmacological properties
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Cellular component annotation derived from the UniProt subcellular location vocabulary. Stilbene synthase is a soluble cytosolic enzyme; resveratrol biosynthesis occurs in the cytoplasm where the phenylpropanoid precursor 4-coumaroyl-CoA and malonyl-CoA are available.
Reason: Consistent with the UniProt SUBCELLULAR LOCATION ("Cytoplasm") and with the general biology of type III polyketide synthases, which are soluble cytosolic enzymes. The annotation is appropriately general and accurate. Cytoplasm is a reasonable, conservative location term; a more specific term (cytosol) could be used but is not required.
Supporting Evidence:
UniProt:P51071
SUBCELLULAR LOCATION: Cytoplasm.
file:VITVI/STS3/STS3-deep-research-falcon.md
Direct immunolocalization and immunogold electron microscopy in young grape plants localized STS protein predominantly to the **cytoplasm and cell wall**, with additional signal observed in **chloroplasts and vacuoles**.
|
|
GO:0016746
acyltransferase activity
|
IEA
GO_REF:0000002 |
MARK AS OVER ANNOTATED |
Summary: Broad molecular function term assigned by InterPro2GO from the thiolase-like / chalcone-stilbene synthase domain signatures (IPR016039, IPR018088). STS3 is an acyltransferase, so the term is correct but generic.
Reason: GO:0016746 "acyltransferase activity" is a correct but very high-level grandparent of the precise activity. STS3 has a specifically defined, experimentally characterized activity (trihydroxystilbene synthase activity, GO:0050350, EC 2.3.1.95) that is also annotated on this protein. The broad parent term adds no information beyond the precise term and is an over-annotation relative to what is known. It is not wrong, so it is marked as over-annotated rather than removed; the precise child term GO:0050350 should be retained as the representative MF.
Supporting Evidence:
UniProt:P51071
Reaction=4-coumaroyl-CoA + 3 malonyl-CoA + 3 H(+) = trans-resveratrol + 4 CO2 + 4 CoA
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|
GO:0016747
acyltransferase activity, transferring groups other than amino-acyl groups
|
IEA
GO_REF:0000002 |
MARK AS OVER ANNOTATED |
Summary: Molecular function term assigned by InterPro2GO from the type III polyketide synthase signature (IPR011141). This is the direct parent of GO:0050350 "trihydroxystilbene synthase activity".
Reason: GO:0016747 is correct (STS3 transfers a malonyl/acyl group, not an amino-acyl group) and is the immediate parent of the precise term GO:0050350, which is also annotated on this protein. Because the precise child term fully captures the activity and EC 2.3.1.95, this broad parent is redundant and represents an over-annotation in terms of specificity. Marked as over-annotated rather than removed because it is taxonomically/biochemically accurate; GO:0050350 should be retained as the core MF.
Supporting Evidence:
UniProt:P51071
EC=2.3.1.95
|
|
GO:0050350
trihydroxystilbene synthase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Precise molecular function term: trihydroxystilbene (resveratrol) synthase activity, EC 2.3.1.95. This is the defining catalytic activity of STS3 and matches the UniProt catalytic activity (Rhea:RHEA:11936) exactly: 4-coumaroyl-CoA + 3 malonyl-CoA + 3 H+ = trans-resveratrol + 4 CO2 + 4 CoA.
Reason: This is the correct, maximally specific molecular function for STS3 and is the representative core MF of the gene. It is fully consistent with the UniProt RecName ("Stilbene synthase 3", "Resveratrol synthase 3", "Trihydroxystilbene synthase 3"), EC 2.3.1.95, the Rhea reaction, the UniPathway entry, and with functional characterization of grapevine STS genes showing they encode bona fide STS activity. The IEA mapping from EC to GO is appropriate and well-supported.
Supporting Evidence:
UniProt:P51071
Reaction=4-coumaroyl-CoA + 3 malonyl-CoA + 3 H(+) = trans-resveratrol + 4 CO2 + 4 CoA; Xref=Rhea:RHEA:11936
PMID:22961129
Functional characterization of nine genes representing most of the STS gene family diversity clearly indicated that these genes do encode for proteins with STS activity
PMID:15309535
The phytoalexin resveratrol (trans-3,5,4'-trihydroxy-stilbene), a natural component of resistance to fungal diseases in many plants, is synthesized by the enzyme trihydroxystilbene synthase (stilbene synthase, EC 2.3.1.95)
|
|
GO:0009811
stilbene biosynthetic process
|
IEA
GO_REF:0000120 |
NEW |
Summary: STS3 is the committed enzyme of stilbene biosynthesis: it forms the resveratrol stilbene backbone from a phenylpropanoid starter and malonyl-CoA. There is currently no biological-process annotation for STS3 in the current GOA release (the retired SPKW GO:0006952 "defense response" annotation was the only BP, and it was an over-annotation). GO:0009811 "stilbene biosynthetic process" is the precise and accurate BP, capturing the enzyme's role without conflating it with the downstream defense function.
Reason: Proposed to replace the over-broad/over-annotated retired GO:0006952 "defense response" SPKW annotation. GO:0009811 is the precise process for the resveratrol backbone-forming reaction and is directly supported by the UniProt PATHWAY line ("Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis"). The closely related GO:0052315 "phytoalexin biosynthetic process" would additionally and legitimately capture the defense context (it is a child of both secondary metabolite biosynthetic process and toxin biosynthetic process) and could be annotated alongside GO:0009811.
Proposed replacements:
stilbene biosynthetic process
phytoalexin biosynthetic process
Supporting Evidence:
UniProt:P51071
PATHWAY: Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis; 3,4',5-trihydroxystilbene from trans-4-coumarate: step 2/2.
PMID:22961129
Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene backbone
file:VITVI/STS3/STS3-deep-research-falcon.md
STS genes encode the enzyme that performs the **terminal committed step** to generate **resveratrol**, positioning STS as a key control point determining whether phenylpropanoid precursors are diverted into **stilbenoids** versus other branches
|
|
GO:0052315
phytoalexin biosynthetic process
|
IEA
GO_REF:0000120 |
NEW |
Summary: Resveratrol synthesized by STS3 is the major stilbenoid phytoalexin of grapevine. GO:0052315 "phytoalexin biosynthetic process" captures the defense-relevant biological context of STS3 accurately, as a biosynthetic-process term (it is a child of both GO:0044550 secondary metabolite biosynthetic process and GO:0009403 toxin biosynthetic process) rather than as a defense-effector term.
Reason: Proposed alongside GO:0009811 as the appropriate replacement for the retired, over-annotated GO:0006952 "defense response" SPKW annotation. It conveys that the stilbene product is a defense compound (phytoalexin) without misrepresenting the enzyme as a pathogen-sensing or defense-response effector. Supported by the UniProt PATHWAY line ("Phytoalexin biosynthesis") and by the consistent literature description of resveratrol/stilbenes as antimicrobial phytoalexins induced by biotic stress.
Supporting Evidence:
UniProt:P51071
PATHWAY: Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis; 3,4',5-trihydroxystilbene from trans-4-coumarate: step 2/2.
PMID:23116673
Stilbenic compounds are natural phytoalexins that have antimicrobial activities in plant defense against pathogens. Stilbene synthase (STS) is the key enzyme that catalyzes the biosynthesis of stilbenic compounds
PMID:15359598
When present, stilbene synthase leads to the production of resveratrol compounds, which are major components of the phytoalexin response against fungal pathogens of the plant
|
Q: Among the ~48 grapevine STS paralogs, do individual members (such as STS3/P51071) have distinct substrate preferences, kinetic properties, or product profiles, or are they functionally redundant?
Q: Is STS3 (VIT_16s0100g01030) expressed and stress-inducible in planta, and in which tissues, given that P51071 evidence is currently only at transcript level (PE 2)?
Experiment: Recombinantly express and purify STS3 (P51071) and assay trihydroxystilbene synthase activity in vitro with 4-coumaroyl-CoA and malonyl-CoA, confirming trans-resveratrol production by LC-MS and measuring kinetic parameters; test alternative phenylpropanoid-CoA starters to define substrate scope.
Experiment: Determine the crystal structure of STS3 (or AlphaFold-guided mutagenesis of the aldol-switch/FGPG loop residues) to confirm the structural basis of aldol versus Claisen cyclization specificity relative to grapevine chalcone synthase.
Experiment: Quantify STS3-specific transcript and protein levels and resveratrol accumulation in grapevine tissues challenged with powdery mildew (Erysiphe necator) or treated with UV/elicitors, to establish the stress-inducible expression profile of this specific paralog.
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.
STS3 (VvSTS3) encodes a type III polyketide synthase (stilbene synthase/resveratrol synthase) that catalyzes the committed step in the stilbenoid branch of the phenylpropanoid pathway, producing trans-resveratrol, a major grapevine phytoalexin involved in stress/defense responses. The enzyme is strongly inducible by stress (e.g., UV-C), and STS gene-family expression is coordinated by MYB and WRKY transcription factors that reprogram carbon flux into stilbenoid biosynthesis. Evidence from immunolocalization places STS protein largely in the cytoplasm and cell wall, with signal also detected in chloroplasts and vacuoles, and enriched in phloem tissues. STS3 has been implemented as an engineering part for extracellular resveratrol production in heterologous plant cell cultures and as a controlled “resveratrol source” in systems investigating resveratrol export/transport. (wang2010distributionofresveratrol pages 4-6, valletta2021impactofenvironmental pages 2-6, vannozzi2018combinatorialregulationof pages 1-4, orduna2022directregulationof pages 12-13, hidalgo2017silybummarianumcell pages 7-10, martinezmarquez2023thegrapevineabc pages 22-26)
The symbol STS3 is used in grapevine literature to denote Vitis vinifera stilbene synthase 3 (VvSTS3). This is supported by studies that explicitly use VvSTS3 as a transgene and report resveratrol production attributable to the introduced gene, including (i) stable expression of a 1179 bp VvSTS3 coding region in Silybum marianum cells and (ii) modular constructs such as pHYH::VvSTS3 and pDGB-VvSTS3 used in grapevine cell assays. These sources align with the UniProt target description (stilbene/resveratrol synthase; type III PKS), supporting that the relevant “STS3” in this evidence corpus is the grapevine stilbene synthase rather than an unrelated gene sharing the STS3 symbol in other organisms. (hidalgo2017silybummarianumcell pages 7-10, martinezmarquez2023thegrapevineabc pages 22-26)
Stilbene synthase (STS), also called resveratrol synthase or trihydroxystilbene synthase, is a type III polyketide synthase (PKS) that forms a stilbene scaffold by condensing one phenylpropanoid-CoA starter with three malonyl-CoA extender units. For grapevine-type “resveratrol synthases,” the canonical reaction is:
This is the core biochemical definition of STS activity used in recent summaries of stilbene biosynthesis. (valletta2021impactofenvironmental pages 2-6)
A comprehensive review notes that grapevine has a large STS multigene family and that while paralogs may differ, clear experimental evidence demonstrating distinct substrate specificities among grape STS paralogs remains limited. The same review highlights proposals for alternative products (e.g., possible piceatannol formation from caffeoyl-CoA), but emphasizes that the dedicated enzyme(s) for such alternative routes are not firmly identified, motivating caution when assigning paralog-specific substrate preferences without direct biochemical assays. (dubrovina2017regulationofstilbene pages 2-4)
STS genes encode the enzyme that performs the terminal committed step to generate resveratrol, positioning STS as a key control point determining whether phenylpropanoid precursors are diverted into stilbenoids versus other branches (e.g., flavonoids via chalcone synthase). (dubrovina2017regulationofstilbene pages 2-4, chialva2018differentialexpressionpatterns pages 1-2)
In grapevine, trans-resveratrol and derived stilbenoids are widely treated as phytoalexins—defense-associated metabolites whose synthesis is induced by biotic and abiotic stress. Regulation studies and stress-induction experiments support this defense-associated role by showing strong inducibility of STS expression and resveratrol accumulation under stress conditions. (wang2010distributionofresveratrol pages 4-6, vannozzi2018combinatorialregulationof pages 1-4, valletta2021impactofenvironmental pages 2-6)
Direct immunolocalization and immunogold electron microscopy in young grape plants localized STS protein predominantly to the cytoplasm and cell wall, with additional signal observed in chloroplasts and vacuoles. Tissue-level localization showed STS signal in multiple organs and highlighted enrichment in phloem tissues, consistent with a model in which resveratrol biosynthesis is positioned in tissues relevant to defense and/or transport interfaces. (Wang et al., 2010, Plant Physiology and Biochemistry, published Feb 2010; https://doi.org/10.1016/j.plaphy.2009.12.002) (wang2010distributionofresveratrol pages 4-6)
STS and resveratrol are strongly inducible by UV-C, with a time-resolved response. In grape leaves, UV-C exposure induced resveratrol accumulation beginning by 8 h and reaching peaks at approximately 196.43× (16 h) and 180.93× (24 h) relative to control, tracking biphasic induction patterns of STS mRNA and STS protein. This provides quantitative evidence that STS induction can be rapid and dramatic under abiotic stress. (Wang et al., 2010; https://doi.org/10.1016/j.plaphy.2009.12.002) (wang2010distributionofresveratrol pages 4-6)
Regulatory work supports a framework where subgroup 2 R2R3-MYB transcription factors (notably MYB14/MYB15, and also MYB13) act as central regulators of stilbenoid metabolism, directly binding and regulating numerous STS family genes and also binding upstream pathway steps (shikimate and early phenylpropanoid genes), consistent with “push” control that increases precursor supply while activating STS expression. (Orduña et al., 2022, The Plant Journal, published Mar 2022; https://doi.org/10.1111/tpj.15686) (orduna2022directregulationof pages 12-13)
Complementing this, promoter-activation and network analyses show that WRKY transcription factors can activate STS promoters either alone or in combination with MYB regulators, revealing combinatorial control and STS-promoter specificity within the family. (Vannozzi et al., 2018, Plant and Cell Physiology, published May 2018; https://doi.org/10.1093/pcp/pcy045) (vannozzi2018combinatorialregulationof pages 1-4)
Promoter analyses of grapevine STS genes indicate that regulatory divergence in promoter regions contributes to differential inducibility across closely related STS paralogs, consistent with the idea that the family has diversified to respond to different stimuli/tissues. Elicitor treatments (including methyl jasmonate and cyclodextrin-related treatments) are described as drivers of STS expression changes in cell culture contexts. (Chialva et al., 2018, Plant Molecular Biology Reporter, published Mar 2018; https://doi.org/10.1007/s11105-018-1073-3) (chialva2018differentialexpressionpatterns pages 1-2)
A 2023 preprint used a modular transcriptional unit pHYH::VvSTS3 (also referenced as pDGB-VvSTS3) in grapevine cell systems as a controllable source of trans-resveratrol to test export mechanisms, connecting STS3-driven synthesis to characterization of a candidate transporter (VvABCB15) implicated in trans-resveratrol export. This represents a recent shift from focusing solely on biosynthesis to studying biosynthesis + transport as an integrated functional module. (Martínez-Márquez et al., 2023, bioRxiv, posted Oct 2023; https://doi.org/10.1101/2023.10.20.563313) (martinezmarquez2023thegrapevineabc pages 13-16, martinezmarquez2023thegrapevineabc pages 22-26)
Within the currently retrieved full-text set, no 2024 peer-reviewed primary paper was captured that directly re-characterizes VvSTS3/P51071 itself (sequence-level or biochemical kinetics). The strongest “latest” item directly invoking VvSTS3 constructs in functional experiments is the 2023 bioRxiv work. (martinezmarquez2023thegrapevineabc pages 13-16, martinezmarquez2023thegrapevineabc pages 22-26)
A clear real-world/biotechnology implementation is stable transformation of Silybum marianum cell cultures with Vitis vinifera STS3 (VvSTS3). The engineered line produced extracellular trans-resveratrol upon elicitation (not detected in biomass), supporting a strategy for production and recovery from culture media. (Hidalgo et al., 2017, Engineering in Life Sciences, published Jun 2017; https://doi.org/10.1002/elsc.201600241) (hidalgo2017silybummarianumcell pages 7-10)
The 2023 STS3 + transporter study reports an approximately 1.9-fold enhancement in a trans-resveratrol transport/export readout when the transporter (VvABCB15) is expressed in an STS3 production context, supporting the applied concept that production traits can be improved by engineering transport/secretion alongside biosynthesis. (Martínez-Márquez et al., 2023; https://doi.org/10.1101/2023.10.20.563313) (martinezmarquez2023thegrapevineabc pages 13-16)
Across primary and review sources, STS enzymes are consistently defined as the committed step generating the resveratrol scaffold from p-coumaroyl-CoA and malonyl-CoA units, and grapevine STS genes are treated as a diversified multigene family deployed for defense- and development-linked responses. The best-supported interpretation is that STS3 (P51071) functions as a canonical resveratrol-forming STS participating in inducible phytoalexin biosynthesis rather than a specialized enzyme with proven unique substrate selectivity. (valletta2021impactofenvironmental pages 2-6, dubrovina2017regulationofstilbene pages 2-4)
The combined MYB/WRKY promoter-control literature supports a mechanistic view that grapevine can “rewire” phenylpropanoid flux toward stilbenoids via transcription factors that simultaneously: (i) activate many STS genes, and (ii) bind upstream pathway genes supplying precursors, with WRKY factors providing promoter specificity and combinatorial modulation. This is consistent with systems-level regulation of specialized metabolism rather than single-gene control. (vannozzi2018combinatorialregulationof pages 1-4, orduna2022directregulationof pages 12-13)
The following table compiles the most directly supported claims for STS3 functional annotation, including URLs and publication years.
| Topic | Key evidence/summary | Best sources |
|---|---|---|
| Identity / synonyms | The target is Vitis vinifera stilbene synthase 3, commonly written as VvSTS3 or STS3, within the grapevine STS multigene family. Direct linkage of VvSTS3 to a grapevine stilbene synthase is supported by a 1179 bp VvSTS3 coding region used in heterologous-expression work and by later construct-based studies using pHYH::VvSTS3 and pDGB-VvSTS3. 2017: https://doi.org/10.1002/elsc.201600241; 2023: https://doi.org/10.1101/2023.10.20.563313 | (hidalgo2017silybummarianumcell pages 7-10, martinezmarquez2023thegrapevineabc pages 22-26) |
| Reaction & substrates | STS, also called resveratrol synthase, is a type III polyketide synthase assigned EC 2.3.1.95. It forms the stilbene skeleton from one cinnamoyl-type CoA ester plus three malonyl-CoA molecules; in grapevine the canonical reaction is p-coumaroyl-CoA plus 3 malonyl-CoA to trans-resveratrol, and current reviews note no clear experimental proof of paralog-specific substrate differences among grape STSs. 2017: https://doi.org/10.1007/s00425-017-2730-8; 2021: https://doi.org/10.3390/plants10010090 | (valletta2021impactofenvironmental pages 2-6, dubrovina2017regulationofstilbene pages 2-4) |
| Pathway role | STS is the terminal committed enzyme of the stilbenoid branch of the phenylpropanoid pathway and produces trans-resveratrol, a principal grapevine stilbene phytoalexin. Regulatory studies further indicate that MYB factors activating STS genes also bind upstream shikimate and early phenylpropanoid genes, consistent with coordinated flux control toward stilbenoid biosynthesis. 2017: https://doi.org/10.1007/s00425-017-2730-8; 2022: https://doi.org/10.1111/tpj.15686 | (dubrovina2017regulationofstilbene pages 2-4, orduna2022directregulationof pages 12-13) |
| Regulation | Grapevine STS genes are inducible by stress and elicitors including UV-C, methyl jasmonate, and cyclodextrin-related treatments. Experimental regulatory evidence shows VviMYB14 and VviMYB15 activate STS promoters, WRKY factors can activate specific STS promoters alone or with MYB14, and VvWRKY8 represses stilbene synthase genes through interaction with MYB14. 2018: https://doi.org/10.1093/pcp/pcy045; 2022: https://doi.org/10.1111/tpj.15686; 2018: https://doi.org/10.1007/s11105-018-1073-3 | (vannozzi2018combinatorialregulationof pages 1-4, orduna2022directregulationof pages 12-13, chialva2018differentialexpressionpatterns pages 1-2) |
| Localization | Immunolocalization in young grape plants placed STS protein in the cytoplasm and cell wall, with signal also observed in chloroplasts and vacuoles, and tissue-level enrichment in phloem. These data support a defense-associated localization pattern in tissues where stilbene accumulation is relevant. 2010: https://doi.org/10.1016/j.plaphy.2009.12.002 | (wang2010distributionofresveratrol pages 4-6) |
| Applications / implementation | VvSTS3 has been used as a functional resveratrol-production module in heterologous plant cell systems and transient grapevine cell assays. Stable expression in Silybum marianum enabled extracellular trans-resveratrol production after elicitation, and 2023 transport studies combined pHYH::VvSTS3 with VvABCB15 to test trans-resveratrol export from grapevine cells. 2017: https://doi.org/10.1002/elsc.201600241; 2023: https://doi.org/10.1101/2023.10.20.563313 | (hidalgo2017silybummarianumcell pages 7-10, martinezmarquez2023thegrapevineabc pages 13-16, martinezmarquez2023thegrapevineabc pages 22-26) |
| Quantitative data | In grape leaves, UV-C caused resveratrol accumulation from 8 h onward, peaking at about 196.43-fold and 180.93-fold over control at 16 h and 24 h, respectively, alongside biphasic STS mRNA and protein induction. In VvSTS3-expressing Silybum marianum cultures, 30 mM cyclodextrin elicitation yielded about 12 mg/L trans-resveratrol at 76 h, and 2023 transporter assays reported an approximately 1.9-fold enhancement in transported or extracellular trans-resveratrol relative to controls. 2010: https://doi.org/10.1016/j.plaphy.2009.12.002; 2017: https://doi.org/10.1002/elsc.201600241; 2023: https://doi.org/10.1101/2023.10.20.563313 | (wang2010distributionofresveratrol pages 4-6, hidalgo2017silybummarianumcell pages 7-10, martinezmarquez2023thegrapevineabc pages 13-16) |
Table: This table condenses the best-supported functional annotation points for Vitis vinifera STS3 (UniProt P51071), including identity, biochemical role, regulation, localization, applications, and quantitative evidence. It only includes claims supported by the retrieved evidence snippets and cites the corresponding context IDs.
References
(wang2010distributionofresveratrol pages 4-6): Wei Wang, Ke Tang, Hao-Ru Yang, Peng-Fei Wen, Ping Zhang, Hui-Ling Wang, and Wei-Dong Huang. Distribution of resveratrol and stilbene synthase in young grape plants (vitis vinifera l. cv. cabernet sauvignon) and the effect of uv-c on its accumulation. Plant physiology and biochemistry : PPB, 48 2-3:142-52, Feb 2010. URL: https://doi.org/10.1016/j.plaphy.2009.12.002, doi:10.1016/j.plaphy.2009.12.002. This article has 240 citations.
(valletta2021impactofenvironmental pages 2-6): Alessio Valletta, Lorenzo Maria Iozia, and Francesca Leonelli. Impact of environmental factors on stilbene biosynthesis. Plants, 10:90, Jan 2021. URL: https://doi.org/10.3390/plants10010090, doi:10.3390/plants10010090. This article has 196 citations.
(vannozzi2018combinatorialregulationof pages 1-4): Alessandro Vannozzi, Darren Chern Jan Wong, Janine H�ll, Ibrahim Hmmam, Jos� Tom�s Matus, Jochen Bogs, Tobias Ziegler, Ian Dry, Gianni Barcaccia, and Margherita Lucchin. Combinatorial regulation of stilbene synthase genes by wrky and myb transcription factors in grapevine (vitis vinifera l.). Plant and Cell Physiology, 59:1043–1059, May 2018. URL: https://doi.org/10.1093/pcp/pcy045, doi:10.1093/pcp/pcy045. This article has 154 citations and is from a domain leading peer-reviewed journal.
(orduna2022directregulationof pages 12-13): Luis Orduña, Miaomiao Li, David Navarro‐Payá, Chen Zhang, Antonio Santiago, Pablo Romero, Živa Ramšak, Gabriele Magon, Janine Höll, Patrick Merz, Kristina Gruden, Alessandro Vannozzi, Dario Cantu, Jochen Bogs, Darren C. J. Wong, Shao‐shan Carol Huang, and José Tomás Matus. Direct regulation of shikimate, early phenylpropanoid, and stilbenoid pathways by subgroup 2
(hidalgo2017silybummarianumcell pages 7-10): Diego Hidalgo, Ascensión Martínez‐Márquez, Rosa Cusidó, Roque Bru‐Martínez, Javier Palazón, and Purificación Corchete. Silybum marianum cell cultures stably transformed with vitis vinifera stilbene synthase accumulate t‐resveratrol in the extracellular medium after elicitation with methyl jasmonate or methylated β‐cyclodextrins. Engineering in Life Sciences, 17:686-694, Jun 2017. URL: https://doi.org/10.1002/elsc.201600241, doi:10.1002/elsc.201600241. This article has 41 citations and is from a peer-reviewed journal.
(martinezmarquez2023thegrapevineabc pages 22-26): A. Martínez-Márquez, V. Martins, S. Sellés-Marchart, H. Gerós, P. Corchete, and R. Bru-Martínez. The grapevine abc transporter b family member 15 (vvabcb15) is trans-resveratrol transporter out of grapevine cells. BioRxiv, Oct 2023. URL: https://doi.org/10.1101/2023.10.20.563313, doi:10.1101/2023.10.20.563313. This article has 5 citations.
(dubrovina2017regulationofstilbene pages 2-4): A. S. Dubrovina and K. V. Kiselev. Regulation of stilbene biosynthesis in plants. Planta, 246:597-623, Jul 2017. URL: https://doi.org/10.1007/s00425-017-2730-8, doi:10.1007/s00425-017-2730-8. This article has 220 citations and is from a peer-reviewed journal.
(chialva2018differentialexpressionpatterns pages 1-2): Constanza Chialva, Claudio Muñoz, María Miccono, Estefanía Eichler, Luciano Calderón, Humberto Prieto, and Diego Lijavetzky. Differential expression patterns within the grapevine stilbene synthase gene family revealed through their regulatory regions. Plant Molecular Biology Reporter, 36:225-238, Mar 2018. URL: https://doi.org/10.1007/s11105-018-1073-3, doi:10.1007/s11105-018-1073-3. This article has 11 citations and is from a peer-reviewed journal.
(martinezmarquez2023thegrapevineabc pages 13-16): A. Martínez-Márquez, V. Martins, S. Sellés-Marchart, H. Gerós, P. Corchete, and R. Bru-Martínez. The grapevine abc transporter b family member 15 (vvabcb15) is trans-resveratrol transporter out of grapevine cells. BioRxiv, Oct 2023. URL: https://doi.org/10.1101/2023.10.20.563313, doi:10.1101/2023.10.20.563313. This article has 5 citations.
UniProt: P51071 (THS3_VITVI). Stilbene synthase 3 / Resveratrol synthase 3 /
Trihydroxystilbene synthase 3 (StSy 3). EC 2.3.1.95. AltName PSV368.
OrderedLocusNames VIT_16s0100g01030 (chromosome 16). 392 aa, ~42.8 kDa.
STS3 is a type III polyketide synthase (PKS III) of the chalcone/stilbene synthase
family. It catalyzes the iterative condensation of one molecule of p-coumaroyl-CoA
(4-coumaroyl-CoA) with three molecules of malonyl-CoA, followed by an intramolecular
aldol cyclization and decarboxylation, to produce trans-resveratrol
(3,4',5-trihydroxystilbene), the major stilbenoid phytoalexin of grapevine.
UniProt catalytic activity (Rhea:RHEA:11936):
4-coumaroyl-CoA + 3 malonyl-CoA + 3 H+ = trans-resveratrol + 4 CO2 + 4 CoA (EC 2.3.1.95).
UniProt PATHWAY: "Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis;
3,4',5-trihydroxystilbene from trans-4-coumarate: step 2/2."
UniProt SUBUNIT: homodimer. SUBCELLULAR LOCATION: Cytoplasm. INDUCTION: by stress.
UniProt FUNCTION line: "Mediates resistance to pathogens which are sensitive to
stilbenes" (ECO:0000250, i.e. inferred by similarity, not direct evidence for STS3).
STS and CHS are paralogous type III PKS enzymes. They use the same substrates
(p-coumaroyl-CoA + 3 malonyl-CoA) and build the same linear tetraketide
intermediate via a single active-site Cys-His-Asn catalytic triad (the Cys is the
acyl carrier nucleophile; in STS3 the conserved active-site residue is annotated at
position 164, ECO:0000255 PROSITE-ProRule:PRU10023).
The enzymes diverge only at the cyclization step:
- CHS performs a C6→C1 Claisen condensation giving naringenin chalcone (a flavonoid
precursor).
- STS performs an alternative C2→C7 aldol condensation plus decarboxylation giving
the stilbene backbone of resveratrol.
PMID:15380179 — this is the "aldol switch" study; an "aldol switch" hydrogen-bonding
network (the "thioesterase-like" pocket) in STS reorients the terminal carbonyl to
favor aldol over Claisen cyclization.
PMID:10926848
Note: STS3 contains the FGPG loop (sequence ...LFGFGPGLTIE... near residues 367–377).
STS arose from CHS by convergent evolution multiple independent times across
stilbene-producing lineages PMID:22961129.
Unlike most stilbene-producing plants where STS forms small families of 2–5 paralogs,
grapevine has an unusually large STS gene family. Reannotation of the PN40024
reference genome yielded 48 STS genes, ≥32 potentially functional, all encoding
proteins with bona fide STS activity PMID:22961129. STS3 (VIT_16s0100g01030, chromosome 16) is one member of this family;
the family is dominated by purifying selection with no strong evidence of neofunctional
divergence PMID:22961129.
The historically best-characterized grapevine STS gene is Vst1 (also called StSy);
"STS3" / PSV368 / pSV21–pSV25 are early-isolated grape STS cDNAs. The original
P51071 sequence comes from a stress-/elicitor-induced grape (cv. Optima) cDNA library
PMID:1898048.
Resveratrol and its derivatives (piceids, viniferins, pterostilbene) are stilbenic
phytoalexins — antimicrobial secondary metabolites synthesized de novo by the plant
in response to biotic and abiotic stress.
STS3's molecular function is a biosynthetic synthase (trihydroxystilbene synthase).
Its product (resveratrol) is antimicrobial, so the gene is defense-associated, but
"defense response" (GO:0006952) as a biological-process annotation conflates the
downstream protective role of the metabolite with the catalytic activity of the enzyme.
The enzyme does not itself sense pathogens or execute a defense response; it
biosynthesizes a stilbene that happens to be a phytoalexin. The accurate biological
process is stilbene biosynthetic process (GO:0009811) and/or phytoalexin
biosynthetic process (GO:0052315). GO:0052315 "phytoalexin biosynthetic process" is a
child of both secondary metabolite biosynthetic process (GO:0044550) and toxin
biosynthetic process (GO:0009403), and it captures the defense context far more
precisely than the generic GO:0006952 without misrepresenting the enzyme as a defense
effector. This is the classic "biosynthetic-enzyme-labelled-with-the-downstream-process"
over-annotation pattern.
id: P51071
gene_symbol: STS3
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:29760
label: Vitis vinifera
description: >-
STS3 (Stilbene synthase 3 / Resveratrol synthase 3 / Trihydroxystilbene synthase 3,
EC 2.3.1.95) is a cytosolic type III polyketide synthase of the chalcone/stilbene
synthase family in grapevine. It catalyzes the iterative condensation of one molecule
of 4-coumaroyl-CoA (p-coumaroyl-CoA) with three molecules of malonyl-CoA, followed by
an intramolecular aldol (C2->C7) cyclization and decarboxylation, to produce
trans-resveratrol (3,4',5-trihydroxystilbene). Resveratrol is the major stilbenoid
phytoalexin of grapevine and is antimicrobial. STS3 belongs to the unusually large
grapevine STS gene family (~48 genes, >=32 functional), which arose from chalcone
synthase (CHS) by convergent evolution; STS and CHS share identical substrates and a
common linear tetraketide intermediate but diverge in their cyclization chemistry
(STS uses aldol cyclization to form a stilbene; CHS uses Claisen cyclization to form
naringenin chalcone). STS3 is the committed enzyme of stilbene/phytoalexin
biosynthesis and is transcriptionally induced by biotic and abiotic stress.
existing_annotations:
# --- SPKW keyword-mapping annotation (GO_REF:0000043) ---
# Present in the Sept 2025 goa_uniprot_gcrp snapshot (go-db plant.ddb); REMOVED
# from the current (2026) GOA release. Reviewed retrospectively; retired: true.
- term:
id: GO:0006952
label: defense response
evidence_type: IEA
original_reference_id: GO_REF:0000043
retired: true
review:
summary: >-
Retired SPKW (keyword2GO) annotation derived from the UniProt keyword "Plant
defense" / "Stress response". STS3 is genuinely defense-associated because its
product resveratrol is an antimicrobial phytoalexin, but the protein's molecular
function is a biosynthetic synthase, not a defense effector or pathogen sensor.
Annotating the enzyme directly to GO:0006952 "defense response" conflates the
downstream protective role of the metabolite with the catalytic function of the
enzyme.
action: MARK_AS_OVER_ANNOTATED
reason: >-
GOA's removal of this annotation was JUSTIFIED. This is a textbook
process-conflation / "biosynthetic-enzyme-labelled-with-the-downstream-process"
over-annotation: the SPKW pipeline mapped the UniProt "Plant defense" keyword
directly onto the enzyme, but STS3 does not itself sense or respond to pathogens.
It biosynthesizes trans-resveratrol, a stilbene that happens to be a phytoalexin.
The defense-relevant role of STS3 is properly captured by the more specific
biosynthetic-process terms GO:0009811 "stilbene biosynthetic process" and
GO:0052315 "phytoalexin biosynthetic process" (a child of both secondary
metabolite biosynthetic process and toxin biosynthetic process), which convey the
defense context without misrepresenting the enzyme as a defense response gene.
GO:0006952 is too broad and is the wrong granularity for a committed biosynthetic
enzyme. The flag retired:true is retained; GOA was correct to retire the SPKW
keyword2GO pipeline for cellular organisms and to drop this annotation. A more
accurate replacement BP annotation is suggested below as a NEW entry.
supported_by:
- reference_id: PMID:1898048
supporting_text: >-
The mechanisms controlling the induction of stilbene synthase and phenylalanine
ammonia-lyase (PAL), two putative key regulatory enzymes of the biosynthetic
pathway to stilbene phytoalexins
- reference_id: PMID:22961129
supporting_text: >-
Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene
backbone
- reference_id: PMID:22961129
supporting_text: >-
In addition to their participation in defense mechanisms in plants, stilbenes,
such as resveratrol, display important pharmacological properties
# --- Current GOA annotations (2026 release) ---
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
Cellular component annotation derived from the UniProt subcellular location
vocabulary. Stilbene synthase is a soluble cytosolic enzyme; resveratrol
biosynthesis occurs in the cytoplasm where the phenylpropanoid precursor
4-coumaroyl-CoA and malonyl-CoA are available.
action: ACCEPT
reason: >-
Consistent with the UniProt SUBCELLULAR LOCATION ("Cytoplasm") and with the
general biology of type III polyketide synthases, which are soluble cytosolic
enzymes. The annotation is appropriately general and accurate. Cytoplasm is a
reasonable, conservative location term; a more specific term (cytosol) could be
used but is not required.
supported_by:
- reference_id: UniProt:P51071
supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- reference_id: file:VITVI/STS3/STS3-deep-research-falcon.md
supporting_text: >-
Direct immunolocalization and immunogold electron microscopy in young grape
plants localized STS protein predominantly to the **cytoplasm and cell wall**,
with additional signal observed in **chloroplasts and vacuoles**.
- term:
id: GO:0016746
label: acyltransferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
Broad molecular function term assigned by InterPro2GO from the thiolase-like /
chalcone-stilbene synthase domain signatures (IPR016039, IPR018088). STS3 is an
acyltransferase, so the term is correct but generic.
action: MARK_AS_OVER_ANNOTATED
reason: >-
GO:0016746 "acyltransferase activity" is a correct but very high-level grandparent
of the precise activity. STS3 has a specifically defined, experimentally
characterized activity (trihydroxystilbene synthase activity, GO:0050350, EC
2.3.1.95) that is also annotated on this protein. The broad parent term adds no
information beyond the precise term and is an over-annotation relative to what is
known. It is not wrong, so it is marked as over-annotated rather than removed; the
precise child term GO:0050350 should be retained as the representative MF.
supported_by:
- reference_id: UniProt:P51071
supporting_text: >-
Reaction=4-coumaroyl-CoA + 3 malonyl-CoA + 3 H(+) = trans-resveratrol + 4 CO2 +
4 CoA
- term:
id: GO:0016747
label: acyltransferase activity, transferring groups other than amino-acyl groups
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
Molecular function term assigned by InterPro2GO from the type III polyketide
synthase signature (IPR011141). This is the direct parent of GO:0050350
"trihydroxystilbene synthase activity".
action: MARK_AS_OVER_ANNOTATED
reason: >-
GO:0016747 is correct (STS3 transfers a malonyl/acyl group, not an amino-acyl
group) and is the immediate parent of the precise term GO:0050350, which is also
annotated on this protein. Because the precise child term fully captures the
activity and EC 2.3.1.95, this broad parent is redundant and represents an
over-annotation in terms of specificity. Marked as over-annotated rather than
removed because it is taxonomically/biochemically accurate; GO:0050350 should be
retained as the core MF.
supported_by:
- reference_id: UniProt:P51071
supporting_text: 'EC=2.3.1.95'
- term:
id: GO:0050350
label: trihydroxystilbene synthase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
Precise molecular function term: trihydroxystilbene (resveratrol) synthase
activity, EC 2.3.1.95. This is the defining catalytic activity of STS3 and matches
the UniProt catalytic activity (Rhea:RHEA:11936) exactly: 4-coumaroyl-CoA + 3
malonyl-CoA + 3 H+ = trans-resveratrol + 4 CO2 + 4 CoA.
action: ACCEPT
reason: >-
This is the correct, maximally specific molecular function for STS3 and is the
representative core MF of the gene. It is fully consistent with the UniProt
RecName ("Stilbene synthase 3", "Resveratrol synthase 3", "Trihydroxystilbene
synthase 3"), EC 2.3.1.95, the Rhea reaction, the UniPathway entry, and with
functional characterization of grapevine STS genes showing they encode bona fide
STS activity. The IEA mapping from EC to GO is appropriate and well-supported.
supported_by:
- reference_id: UniProt:P51071
supporting_text: >-
Reaction=4-coumaroyl-CoA + 3 malonyl-CoA + 3 H(+) = trans-resveratrol + 4 CO2 +
4 CoA; Xref=Rhea:RHEA:11936
- reference_id: PMID:22961129
supporting_text: >-
Functional characterization of nine genes representing most of the STS gene
family diversity clearly indicated that these genes do encode for proteins with
STS activity
- reference_id: PMID:15309535
supporting_text: >-
The phytoalexin resveratrol (trans-3,5,4'-trihydroxy-stilbene), a natural
component of resistance to fungal diseases in many plants, is synthesized by the
enzyme trihydroxystilbene synthase (stilbene synthase, EC 2.3.1.95)
# --- Suggested NEW annotation (BP not currently captured) ---
- term:
id: GO:0009811
label: stilbene biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
STS3 is the committed enzyme of stilbene biosynthesis: it forms the resveratrol
stilbene backbone from a phenylpropanoid starter and malonyl-CoA. There is
currently no biological-process annotation for STS3 in the current GOA release
(the retired SPKW GO:0006952 "defense response" annotation was the only BP, and it
was an over-annotation). GO:0009811 "stilbene biosynthetic process" is the precise
and accurate BP, capturing the enzyme's role without conflating it with the
downstream defense function.
action: NEW
reason: >-
Proposed to replace the over-broad/over-annotated retired GO:0006952 "defense
response" SPKW annotation. GO:0009811 is the precise process for the resveratrol
backbone-forming reaction and is directly supported by the UniProt PATHWAY line
("Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis"). The closely
related GO:0052315 "phytoalexin biosynthetic process" would additionally and
legitimately capture the defense context (it is a child of both secondary
metabolite biosynthetic process and toxin biosynthetic process) and could be
annotated alongside GO:0009811.
proposed_replacement_terms:
- id: GO:0009811
label: stilbene biosynthetic process
- id: GO:0052315
label: phytoalexin biosynthetic process
supported_by:
- reference_id: UniProt:P51071
supporting_text: >-
PATHWAY: Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis;
3,4',5-trihydroxystilbene from trans-4-coumarate: step 2/2.
- reference_id: PMID:22961129
supporting_text: >-
Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene
backbone
- reference_id: file:VITVI/STS3/STS3-deep-research-falcon.md
supporting_text: >-
STS genes encode the enzyme that performs the **terminal committed step** to
generate **resveratrol**, positioning STS as a key control point determining
whether phenylpropanoid precursors are diverted into **stilbenoids** versus
other branches
- term:
id: GO:0052315
label: phytoalexin biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
Resveratrol synthesized by STS3 is the major stilbenoid phytoalexin of grapevine.
GO:0052315 "phytoalexin biosynthetic process" captures the defense-relevant
biological context of STS3 accurately, as a biosynthetic-process term (it is a
child of both GO:0044550 secondary metabolite biosynthetic process and GO:0009403
toxin biosynthetic process) rather than as a defense-effector term.
action: NEW
reason: >-
Proposed alongside GO:0009811 as the appropriate replacement for the retired,
over-annotated GO:0006952 "defense response" SPKW annotation. It conveys that the
stilbene product is a defense compound (phytoalexin) without misrepresenting the
enzyme as a pathogen-sensing or defense-response effector. Supported by the UniProt
PATHWAY line ("Phytoalexin biosynthesis") and by the consistent literature
description of resveratrol/stilbenes as antimicrobial phytoalexins induced by
biotic stress.
supported_by:
- reference_id: UniProt:P51071
supporting_text: >-
PATHWAY: Phytoalexin biosynthesis; 3,4',5-trihydroxystilbene biosynthesis;
3,4',5-trihydroxystilbene from trans-4-coumarate: step 2/2.
- reference_id: PMID:23116673
supporting_text: >-
Stilbenic compounds are natural phytoalexins that have antimicrobial activities
in plant defense against pathogens. Stilbene synthase (STS) is the key enzyme
that catalyzes the biosynthesis of stilbenic compounds
- reference_id: PMID:15359598
supporting_text: >-
When present, stilbene synthase leads to the production of resveratrol
compounds, which are major components of the phytoalexin response against fungal
pathogens of the plant
core_functions:
- description: >-
Type III polyketide synthase that catalyzes trihydroxystilbene (resveratrol)
synthase activity: it iteratively condenses 4-coumaroyl-CoA with three molecules of
malonyl-CoA and performs an aldol (C2->C7) cyclization with decarboxylation to
produce trans-resveratrol, the committed step of stilbene phytoalexin biosynthesis
in grapevine.
molecular_function:
id: GO:0050350
label: trihydroxystilbene synthase activity
directly_involved_in:
- id: GO:0009811
label: stilbene biosynthetic process
- id: GO:0052315
label: phytoalexin biosynthetic process
locations:
- id: GO:0005737
label: cytoplasm
substrates:
- id: CHEBI:57355
label: 4-coumaroyl-CoA
- id: CHEBI:57384
label: malonyl-CoA
supported_by:
- reference_id: UniProt:P51071
supporting_text: >-
Reaction=4-coumaroyl-CoA + 3 malonyl-CoA + 3 H(+) = trans-resveratrol + 4 CO2 + 4
CoA; Xref=Rhea:RHEA:11936, ... EC=2.3.1.95;
- reference_id: PMID:15380179
supporting_text: >-
Stilbene synthase (STS) and chalcone synthase (CHS) each catalyze the formation of
a tetraketide intermediate from a CoA-tethered phenylpropanoid starter and three
molecules of malonyl-CoA, but use different cyclization mechanisms
- reference_id: file:VITVI/STS3/STS3-deep-research-falcon.md
supporting_text: >-
STS3 (VvSTS3)** encodes a **type III polyketide synthase (stilbene
synthase/resveratrol synthase)** that catalyzes the committed step in the
**stilbenoid branch** of the phenylpropanoid pathway, producing
**trans-resveratrol**, a major grapevine phytoalexin involved in stress/defense
responses
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings:
- statement: InterPro2GO mapping of the chalcone/stilbene synthase and type III
polyketide synthase domain signatures supplied the broad acyltransferase-activity
molecular-function annotations reviewed in this file.
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings:
- statement: SwissProt keyword-derived (SPKW) annotations present in the Sept 2025
goa_uniprot_gcrp snapshot but removed from the current GOA release after GOA
retired the keyword2GO pipeline for cellular organisms.
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings:
- statement: Mapping of the UniProt subcellular location "Cytoplasm" supplied the
cytoplasm cellular-component annotation reviewed in this file.
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings:
- statement: Combined multi-method IEA annotation supplied the precise trihydroxystilbene
synthase activity (GO:0050350, EC 2.3.1.95) molecular-function annotation reviewed
in this file.
- id: file:VITVI/STS3/STS3-deep-research-falcon.md
title: Deep research report (falcon / Edison Scientific) on Vitis vinifera STS3
(P51071) - Stilbene synthase 3 / Resveratrol synthase 3
findings:
- statement: STS3 (VvSTS3) is a type III polyketide synthase (stilbene/resveratrol
synthase, EC 2.3.1.95) that catalyzes the committed step of the stilbenoid branch
of the phenylpropanoid pathway, condensing one p-coumaroyl-CoA starter with three
malonyl-CoA extenders to form trans-resveratrol.
- statement: trans-Resveratrol and derived stilbenoids are treated as phytoalexins -
defense-associated metabolites whose synthesis is strongly induced by biotic and
abiotic stress (e.g., UV-C induced resveratrol accumulation ~196x over control at
16 h, with parallel biphasic induction of STS mRNA and protein); the defense role
is a property of the metabolite product, while the enzyme itself performs a
biosynthetic synthase function.
- statement: STS belongs to a large diversified grapevine multigene family; reviews
emphasize that clear experimental evidence for distinct substrate specificities
among individual grape STS paralogs remains limited, and no 2024 primary paper
directly re-characterizes VvSTS3/P51071 biochemistry.
- statement: Immunolocalization in young grape plants placed STS protein predominantly
in the cytoplasm and cell wall, with additional signal in chloroplasts and
vacuoles and tissue enrichment in phloem, consistent with a soluble cytosolic
enzyme.
- statement: STS family expression is coordinated by subgroup 2 R2R3-MYB (MYB14/MYB15)
and WRKY transcription factors that reprogram carbon flux toward stilbenoid
biosynthesis; VvSTS3 has been used as an engineered resveratrol-production module
in heterologous plant cell systems.
- id: UniProt:P51071
title: UniProtKB entry THS3_VITVI (Stilbene synthase 3, Vitis vinifera)
findings:
- statement: STS3 catalyzes 4-coumaroyl-CoA + 3 malonyl-CoA + 3 H+ = trans-resveratrol
+ 4 CO2 + 4 CoA (EC 2.3.1.95, Rhea:RHEA:11936); it is a cytoplasmic homodimer of
the chalcone/stilbene synthase (thiolase-like) family, induced by stress.
reference_section_type: OTHER
- id: PMID:1898048
title: Coordinate- and elicitor-dependent expression of stilbene synthase and
phenylalanine ammonia-lyase genes in Vitis cv. Optima.
findings:
- statement: Stilbene synthase and PAL are key enzymes of the biosynthetic pathway to
stilbene phytoalexins; their mRNAs are co-induced within 1 h of fungal cell-wall
elicitor treatment of grape cell cultures.
reference_section_type: ABSTRACT
- id: PMID:22961129
title: Structural, functional, and evolutionary analysis of the unusually large
stilbene synthase gene family in grapevine.
findings:
- statement: The grapevine genome contains an unusually large STS gene family (48 STS
genes, >=32 potentially functional); STS evolved from CHS several times
independently, and characterized grapevine STS genes encode bona fide STS
activity.
reference_section_type: ABSTRACT
- id: PMID:15380179
title: An aldol switch discovered in stilbene synthases mediates cyclization
specificity of type III polyketide synthases.
findings:
- statement: STS and CHS use the same phenylpropanoid starter and three malonyl-CoA to
form a common tetraketide intermediate, then use different cyclization mechanisms;
an "aldol switch" in STS directs aldol cyclization to form the stilbene scaffold.
reference_section_type: ABSTRACT
- id: PMID:10426957
title: Structure of chalcone synthase and the molecular basis of plant polyketide
biosynthesis.
findings:
- statement: CHS condenses one p-coumaroyl-CoA and three malonyl-CoA into a polyketide
intermediate that cyclizes; the CHS-resveratrol complex shows how the related
stilbene synthase uses the same substrates and an alternate cyclization pathway.
reference_section_type: ABSTRACT
- id: PMID:23116673
title: Transcriptional expression of Stilbene synthase genes are regulated
developmentally and differentially in response to powdery mildew in Norton and
Cabernet Sauvignon grapevine.
findings:
- statement: STS is the key enzyme of stilbenic phytoalexin biosynthesis; individual
grapevine STS genes are transcriptionally induced by powdery mildew infection and
regulated developmentally.
reference_section_type: ABSTRACT
- id: PMID:15309535
title: Expression of the grapevine stilbene synthase gene VST1 in papaya provides
increased resistance against diseases caused by Phytophthora palmivora.
findings:
- statement: Resveratrol (1 mM) inhibits mycelial growth of Phytophthora palmivora in
vitro; heterologous expression of a grapevine STS gene increases pathogen
resistance in papaya.
reference_section_type: ABSTRACT
- id: PMID:15359598
title: Expression of the stilbene synthase (StSy) gene from grapevine in transgenic
white poplar results in high accumulation of the antioxidant resveratrol glucosides.
findings:
- statement: Grapevine STS expressed in white poplar produces resveratrol glucosides,
but accumulation of the phytoalexin did not increase rust resistance, showing the
STS enzyme is one biosynthetic input rather than a complete defense program.
reference_section_type: ABSTRACT
- id: PMID:31531782
title: Expression of stilbene synthase VqSTS6 from wild Chinese Vitis quinquangularis
in grapevine enhances resveratrol production and powdery mildew resistance.
findings:
- statement: STS expression and stilbenoid levels increase in response to powdery
mildew infection; overexpression of an STS gene raises stilbenoid accumulation and
disease resistance in grapevine.
reference_section_type: ABSTRACT
proposed_new_terms: []
suggested_questions:
- question: >-
Among the ~48 grapevine STS paralogs, do individual members (such as STS3/P51071)
have distinct substrate preferences, kinetic properties, or product profiles, or are
they functionally redundant?
- question: >-
Is STS3 (VIT_16s0100g01030) expressed and stress-inducible in planta, and in which
tissues, given that P51071 evidence is currently only at transcript level (PE 2)?
suggested_experiments:
- description: >-
Recombinantly express and purify STS3 (P51071) and assay trihydroxystilbene synthase
activity in vitro with 4-coumaroyl-CoA and malonyl-CoA, confirming trans-resveratrol
production by LC-MS and measuring kinetic parameters; test alternative
phenylpropanoid-CoA starters to define substrate scope.
- description: >-
Determine the crystal structure of STS3 (or AlphaFold-guided mutagenesis of the
aldol-switch/FGPG loop residues) to confirm the structural basis of aldol versus
Claisen cyclization specificity relative to grapevine chalcone synthase.
- description: >-
Quantify STS3-specific transcript and protein levels and resveratrol accumulation in
grapevine tissues challenged with powdery mildew (Erysiphe necator) or treated with
UV/elicitors, to establish the stress-inducible expression profile of this specific
paralog.