The Scoville Splice Capsaicin Design Platform: A Computational Framework for Receptor-Normalized Cross-Modal Flavor Engineering Using the Iyengar Flavor Index

Version 1.0 — November 2026. This preprint introduces the Scoville Splice Capsaicin Design Platform and the Iyengar Flavor Index (IFI), a receptor-normalized cross-modal potency metric for computational flavor engineering in food crops. The IFI extends the century-old Scoville Heat Unit framework from a single-axis proxy (TRPV1 capsaicin activation) to an eight-dimensional receptor space spanning the full chemosensory repertoire of human flavor perception. THE IYENGAR FLAVOR INDEX The IFI is defined as: IFI(c, m) = 1,000 × EC₅₀(ref, m) / EC₅₀(c, m), where c is the candidate compound or engineered construct, m is the receptor modality, EC₅₀(ref, m) is the half-maximal effective concentration of the canonical reference agonist for modality m, and EC₅₀(c, m) is the predicted EC₅₀ of the candidate at that receptor. A score of 1,000 indicates the candidate matches the reference agonist exactly. The formula is dimensionless, receptor-normalized, and backward-compatible with the Scoville scale: IFI-H equals SHU when the reference is capsaicin at TRPV1. The IFI is named by the convention established by Scoville (1912), Sørensen (1909, pH), and Jenkins & Wolever (1981, Glycemic Index): a receptor-physiological response metric normalized to a reference compound on a dimensionless scale. THE EIGHT RECEPTOR AXES IFI-H: TRPV1 (NCBI Gene ID 7442). Heat/burn perception. Reference: capsaicin, EC₅₀ 3.16 nM (Caterina et al. 1997, Nature 389:816). IFI-H = SHU (backward-compatible). D.N.R. (SS-CV-010) IFI-H: 2,956,310. IFI-S: TAS1R2/TAS1R3 heterodimer (Gene IDs 80834, 83756). Sweet taste. Reference: sucrose, EC₅₀ 34.2 mM (Nelson et al. 2002, Cell 106:381). Brazzein (PbBRZ, 54 aa) in Capsicum background achieves IFI-S ~2,200,000 via TAS1R2/TAS1R3 EC₅₀ ~5 nM (Paper 3, this series). IFI-U: TAS1R1/mGluR1 (Gene IDs 80835, 2911). Umami/savory depth. Reference: L-glutamate (MSG), EC₅₀ 820 µM (Li et al. 2002, PNAS 99:4692; Chaudhari et al. 2000, Nat Neurosci 3:113). GAD1/GAD4 double KO plus AtGDH1 overexpression in Capsicum projects IFI-U ≥ 800 via 8.3× free glutamate accumulation (Paper 5, this series). IFI-B: TAS2R38 (Gene ID 5726). Bitterness suppression axis — IFI-B toward 0 indicates bitterness elimination. Reference: PTC (phenylthiocarbamide), EC₅₀ 1.2 µM (Behrens et al. 2004, BBRC 319:479). TGG1/TGG2 myrosinase double KO in allotetraploid Brassica oleracea reduces IFI-B from ~770 to <40 by eliminating isothiocyanate production (Paper 6, this series). IFI-K: CaSR (Gene ID 846). Kokumi mouthfeel and flavor continuity. Reference: γ-Glu-Val-Gly, EC₅₀ 48 nM (Ohsu et al. 2010, J Biol Chem 285:1016). GCS1 (AtGSH1) overexpression projects IFI-K ≥ 2,400 via γ-glutamyl peptide accumulation (Paper 7, this series). IFI-C: TRPM8/TRPV1 biphasic (Gene IDs 79054, 7442). Cool-burn temperature duality. Reference: menthol:capsaicin composite, EC₅₀ 78 µM (McKemy et al. 2002, Nature 416:52). Five-gene Mentha × piperita menthol pathway reconstitution in Capsicum projects IFI-C ~85,000 at ~85 µg/g FW menthol (Paper 9, this series). IFI-P: TRPA1 (Gene ID 8989). Pungency (wasabi/cinnamon axis). Reference: allyl isothiocyanate (AITC), EC₅₀ 56 µM (Jordt et al. 2004, Nature 427:260). CrCCR1 insertion under E8 promoter projects IFI-P ~170,000 at ~500 µg/g FW cinnamaldehyde (Paper 10, this series). IFI-A: Proanthocyanidin pathway (VvLAR1/VvANR/VvDFR). Astringency. Reference: tannic acid, EC₅₀ 1,100 µg/mL (Bate-Smith 1954). ANR knockout reduces IFI-A from ~600 to <100 in Vitis vinifera; TAN1 knockout from ~1,200 to <80 in Sorghum bicolor (Paper 8, this series). IFI-F (Full Spectrum Composite): geometric mean of all 8 subscale scores, (∏ IFI_i)^(1/8). Used for polypharmacology products targeting multiple receptor axes simultaneously. COMPUTATIONAL METHODOLOGY All IFI scores reported for engineered constructs are computational design targets derived from pathway flux modeling and receptor binding estimation, NOT experimentally measured values. The design pipeline uses COBRApy v0.29 with PlantCoreMetabolism v2.0. Objective functions maximize target metabolite flux (capsaicin, glutamate, menthol, cinnamaldehyde, etc.). Ten stochastic replicates apply Gaussian flux perturbation (σ = 0.1) to non-target fluxes. Predicted metabolite concentrations are mapped to receptor activation via the Hill equation: response = E_max × [A]^n / (EC₅₀^n + [A]^n), with Hill coefficients estimated from primary literature per receptor. Physical transformation, transgene expression, and sensory validation require independent experimental verification. D.N.R. FULL SPECTRUM IFI PROFILE (SS-CV-010 + all 8 series interventions):IFI-H: 2,956,310 | IFI-S: ~2,200,000 | IFI-U: ~820 | IFI-B: ~30 | IFI-K: ~2,400 | IFI-C: ~85,000 | IFI-P: ~170,000 | IFI-A: ~42 LIMITATIONS Stated explicitly: (1) All IFI scores are computational predictions, not measured receptor activation values. (2) FBA models assume steady-state flux and do not capture post-translational regulation, epigenetic silencing, insertion-site effects, or developmental dynamics. (3) Heterologous receptor EC₅₀ values may differ from in vivo oral exposure kinetics. (4) CRISPR guide sequences require experimental off-target validation in the target organism and BSL-appropriate facility. (5) Constructs involving transgenic organisms require IBC review and jurisdiction-specific regulatory approval. This paper is the eleventh in the Scoville Splice Research Series and serves as the platform methodology overview. It introduces the IFI framework that underpins Papers 3–10 of the series. Related records: 10.5281/zenodo.23743695 (Paper 1, main Capsicum cultivars paper), 10.5281/zenodo.23749878 (Paper 2, Beyond Peppers cross-species), 10.5281/zenodo.23873914 (Paper 4, IFI sub-scale calibration). Keywords: Iyengar Flavor Index, IFI, flavor engineering, receptor normalization, TRPV1, TAS1R2/TAS1R3, mGluR1, TAS2R38, CaSR, TRPM8, TRPA1, proanthocyanidin, Capsicum annuum, CRISPR, flux balance analysis, computational plant biology, synthetic biology, cross-modal flavor, chemosensory receptors