Saccharomyces Met-Trp4 FLO1 Resveratrol Coculture

A defined two-member synthetic Saccharomyces cerevisiae coculture that combines Met-Trp4 coauxotrophic cross-feeding, FLO1-mediated cell adhesion, and division of labor across the de novo resveratrol pathway. In the Met-Trp4 A-B:FLO1 configuration, a met14 knockout derivative of the nonflocculating 007 deletion background carries the FjTAL upstream module that converts L-tyrosine to p-coumaric acid, while a trp4 knockout partner carries the At4CL and VvVST1 downstream module that converts p-coumaric acid to resveratrol. After 48 h in SM medium, the FLO1 adhesion variant produced more resveratrol than the no-FLO1 Met-Trp4 A-B coculture, noncross-feeding controls, and a monoculture carrying the full pathway.

Taxonomy

Taxon Ontology ID Functional Roles Abundance
Saccharomyces cerevisiae 007 met14 module A FLO1 cell 1 — ontology label: Saccharomyces cerevisiae NCBITaxon:4932 · TaxonMech · TraitMech
CROSS_FEEDER
COMMON
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Cell 1: lys2Δ (trp2Δ or met14Δ) sfGFP; Cell 2: ade8Δ (or trp4Δ) mRuby2"
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "The superscript ‘A–B’ denotes module A in cell 1 and module B in cell 2"
Saccharomyces cerevisiae 007 trp4 module B FLO1 cell 2 — ontology label: Saccharomyces cerevisiae NCBITaxon:4932 · TaxonMech · TraitMech
CROSS_FEEDER
COMMON
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Cell 1: lys2Δ (trp2Δ or met14Δ) sfGFP; Cell 2: ade8Δ (or trp4Δ) mRuby2"
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "The superscript ‘A–B’ denotes module A in cell 1 and module B in cell 2"

Ecological Interactions

The graph shows only explicitly linked interaction participants. Community members without an asserted participant link are omitted; membership alone does not imply an interaction.

Ecological interaction network for Saccharomyces Met-Trp4 FLO1 Resveratrol Coculture Bipartite graph where circles represent taxa and non-circular symbols represent interactions, with distinct shapes and colours for cross-feeding, mutualism. Rare or untyped interactions share the Other symbol; exact curated types remain in the interaction details.
Taxon
Cross-feeding
Mutualism
Other

Met-Trp4 Coauxotrophic Cross-Feeding

MUTUALISM

The Met-Trp4 coauxotrophic yeast pair forms a mutually dependent growth system in the tested medium lacking the complementary required nutrients. This growth relationship is distinct from the resveratrol pathway handoff and does not by itself establish enhanced product titer or unconditional dependence in supplemented environments.

Participating Taxa: Saccharomyces cerevisiae 007 met14 module A FLO1 cell 1, Saccharomyces cerevisiae 007 trp4 module B FLO1 cell 2

Evidence

  • PMID:41491832 - SUPPORT (IN_VITRO)
    "two auxotrophic cells, cell 1 and cell 2, must be present simultaneously to form cross-feeding for growth"

Resveratrol Pathway Division of Labor

CROSS_FEEDING

The existing met14 module-A and trp4 module-B partners divide the resveratrol pathway around p-coumaric acid. The reported module assignment and product/intermediate measurements support the intended metabolic handoff, but do not directly quantify intercellular transfer flux or show that it alone explains the FLO1-associated production increment.

Source Taxon: Saccharomyces cerevisiae 007 met14 module A FLO1 cell 1

Target Taxon: Saccharomyces cerevisiae 007 trp4 module B FLO1 cell 2

Metabolites: p-coumaric acid (CHEBI:32374 · MediaIngredientMech · CMMMech)

Downstream Effects:
→ FLO1 Adhesion-Enhanced Resveratrol Production

PARTIAL: the divided pathway supplies the precursor-to-product route in the tested FLO1 coculture, enabling resveratrol synthesis. It does not independently explain the increase over the no-FLO1 control; adhesion-dependent transfer efficiency was not isolated as the mediator.

Evidence

  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Module A contained FjTAL, catalyzing L-tyrosine to p-coumaric acid, while module B contained At4CL and VvVST1, converting p-coumaric acid to resveratrol"

FLO1 Adhesion-Enhanced Resveratrol Production

The tested Met-Trp4 A-B:FLO1 coculture produced more resveratrol than its no-FLO1 counterpart, the corresponding FLO1 noncross-feeding control and the full-pathway monoculture. This is an aggregate production endpoint, not by itself a mutualistic fitness measurement. The higher titer co-occurred with precursor accumulation and lower biomass in this configuration; it does not establish more efficient precursor conversion or a universal benefit of adhesion across yeast pairs.

Participating Taxa: Saccharomyces cerevisiae 007 met14 module A FLO1 cell 1, Saccharomyces cerevisiae 007 trp4 module B FLO1 cell 2

Evidence

  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Notably, the pair Met-Trp4, in the presence of FLO1, always increased production"
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Met–Trp4A–B:FLO1 produced 0.67 μM of resveratrol, a 2.47-fold increase compared to Mctrl"

Knowledge gaps & discussions (1)

KNOWLEDGE_GAP OPEN How much of the FLO1-associated titer increment is mediated by intercellular precursor transfer?

The production comparison and coauxotrophic mutualism are supported, but neither an endpoint titer nor pathway assignment independently measures transfer efficiency or reciprocal fitness. The source explicitly leaves aggregate morphology and metabolic exchange for further study. Preserve the one existing direction as PARTIAL, without restoring the previously removed growth-background arrow.

Attaches to: ecological_interactions#Met-Trp4 Coauxotrophic Cross-Feeding, ecological_interactions#Resveratrol Pathway Division of Labor, ecological_interactions#FLO1 Adhesion-Enhanced Resveratrol Production

1 evidence item(s)
IN_VITRO SUPPORT PMID:41491832

Systematic investigation of aggregate morphology and its impact on metabolic exchange represents an important direction for future research

The authors distinguish their demonstrated production endpoint from unresolved exchange mechanisms.

External Resources

Name Repository Resource ID
Primary article - programmable yeast adhesion resveratrol coculture
Nature Chemical Biology article reporting the engineered FLO1 Met-Trp4 S. cerevisiae resveratrol coculture.
OTHER doi:10.1038/s41589-025-02081-1
  • PMID:41491832 - SUPPORT (IN_VITRO)
    "Programmable cell-cell adhesion in synthetic yeast communities for improved bioproduction"

Growth Media

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