Grant E DuBoisAdvances in the Science of Sweet Taste & Sweetness Enhancement
2 Advances in the Science of Sweet Taste & Sweetness Enhancement Grant E DuBois Research Fellow The Coca-Cola Company Atlanta, GA USA The Coca-Cola Company
3 Outline I. Sensing Foods and Beverages II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today IV. Sweetener Receptor Positive Allosteric Modulators, a Novel Approach to Sugar-Like Taste The Coca-Cola Company
The Coca-Cola Company 4 I. Sensing Foods & Beverages: Gustation
The Coca-Cola Company 5 Gustation: A Superimposition of 5 Taste Modalities Sweet Bitter Umami Salty Sour
The Coca-Cola Company 6 The Biology of Gustation
The Coca-Cola Company 7 Lingual Taste Buds are Found in Papillae
8 Are You a Non-Taster, a Taster or a Supertaster? Linda Bartoshuk, U of Florida The Coca-Cola Company
The Coca-Cola Company 9 What Do Taste Buds and Taste Bud Cells Look Like? M. Behrens, W. Meyerhof, C. Hellfritsch and T. Hofmann, Angew. Chem. Int. Ed., 2011, 50, 2220-2242.
10 How do Sweeteners, Bitterants and Savory Compounds Excite Taste Bud Cells? Saliva Na+ Na+ Na+ Sweetener/ Bitterant/ Savory Compound Na+ Receptor Na+ TRP Channel Electrical Message to Brain Phospholipase C Gg Gb IP2 IP3 Ca2+ Ga Cytosol ~-60mV GDP Gg Gb GTP Endoplasmic Reticulum The Coca-Cola Company
The Coca-Cola Company 11 What does the Sweetener Receptor Look Like and How does Sugar Activate it? Sucrose T1R2 T1R3
12 II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers The Coca-Cola Company
13 Key Message: In order to realize outstanding commercial success, a new sweetness technology must deliver on all of the metrics........Safety, Taste Quality, Stability, Solubility and Cost…… and without compromise on Safety or Taste Quality. The Coca-Cola Company
14 Commercial Viability is Dependent on 6 Metrics Safety Taste Quality
C/R Function & Rm
Stability Solubility Cost Patentability G. E. DuBois, “Sweeteners and Sweetness Modulators: Requirements for Commercial Viability”, Chapter 29 in Sweetness and Sweeteners, G E DuBois and D Weerasinghe, Eds., ACS Symposium Series 979, ACS Books, Washington DC, 2008. The Coca-Cola Company
15 III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today The Coca-Cola Company
16 Key Messages: 1. HP sweeteners known today do not match the Taste Quality of sugar……….anddelivery on the Taste Quality metric requires “Sweetness Modulators”; and 2. Since trial-and-error approaches have been employed for saccharin (>100 years) and aspartame (~30 years) w/o significant progress……..a new paradigm……..a Mechanism of Action (MOA) based paradigm………is needed to find effective “Sweetness Modulators”. The Coca-Cola Company
MOA Approach to Rebaudioside A Sweetness Modulators Operating Principle: The non-sugar-like taste of REBA is intrinsically linked to its chemical structure! 17 The Coca-Cola Company
MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d)
Maruzen Pharmaceutical Company: NaCl found to cause a 2.5-fold increase in potency of stevia sweeteners.
The Coca-Cola Company: NaCl, and/or other osmolytes, found to cause increases in sweetness potencies as well as elimination of the slow sweetness onset and the sweetness linger for Rebaudioside A and other HP sweeteners thus leading to the Non-Specific Binding Hypothesis.1, 2
1. I. Prakash, G. E. DuBois, P. Jella, G. A. King, R. I. San Miguel, K. H. Sepcic, D. K. Weerasinghe, N. R. White, US Patent Application 20070128311 (June 7, 2007). 2. G. DuBois, “Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models” Flavour and Fragrance Journal 2011, Electronic Version: wileyonlinelibrary.com (DOI 10.1002/ffj.2042), Print Version: July-August Issue.
Keiko Abe Laboratory (University of Tokyo): Support for the Non-Specific Binding Hypothesis as the rationale for slow sweetness onset and sweetness linger.3
3. K. Abe, et al., “Surface Plasmon Resonance Analysis on Interactions of Food Components with a Taste Epithelial Cell Model”, J. Agric. Fd. Chem. 2010, 58 (22), 11870-11875. 18 The Coca-Cola Company
MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d) 19 The Coca-Cola Company Rebaudioside A (500mg/L) / Osmolyte Formulations
20 IV. Sweetener Receptor Positive Allosteric Modulators(aka Sweetness Enhancers), a Novel Approach to Sugar-Like Tasteat Lower Calories The Coca-Cola Company
21 Key Message: Sweetener receptor positive allosteric modulators (PAMs)…..……aka enhancers…….which potentiate the activities of carbohydrate sweeteners enable accurate reproduction of carbohydrate sweetener taste quality w/ dramatic reduction in caloric content. The Coca-Cola Company
Sweetener Receptor Positive Allosteric Modulators An Early Conceptual View of the Function of a Positive Allosteric Modulator (PAM) in the Sweetener Receptor 22 Sucrose Signal: 1 PAM Sucrose Signal: >>1 Signal: 0 Signal: 0 The Coca-Cola Company
Proof of Concept for Sweetness Enhancement 23 DHB 2001: @ 375 mg/L, DHB enhances 6% sucrose to 8% sucrose w/o any off taste! A weaker effect was noted for fructose and no effect for glucose. G. DuBois, “Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models” Flavour and Fragrance Journal 2011, Electronic Version: wileyonlinelibrary.com (DOI 10.1002/ffj.2042), Print Version: July-August Issue. The Coca-Cola Company
Senomyx Collaboration: PAM Discovery by HTS / Cell-Based Assay 24 ~8-Fold Sucralose Enhancer ~2-Fold Sucrose Enhancer G. Servant, C. Tachdjian, X. Tang, S. Werner, F. Zhang, X. Li, P. Kamdar, G. Petrovic, T. Ditschun, A. Java, P. Brust, N. Brune, G. E. DuBois, M. Zoller and D. S. Karanewsky, Proc. Natl. Acad. Sci. USA, 2010, 107, 4746-4751. R. Shigemura, C. Podgurski, B. Kitisin, J. Ward, A. Alatorre, PCT Patent Application No. WO2010/014813 A2 (February 4, 2010). The Coca-Cola Company
25 MOA for PAM Activity at the Sweetener Receptor Adapted from S. D. Munger et al. The Coca-Cola Company
Sweetener Receptor PAMs 26
Original Hypothesis: CHO Sweetener / PAM formulations will taste equivalent to CHO Sweeteners (i.e., not be limited by low Rm, bitter, metallic, licorice, etc. off tastes, slow sweetness onset / sweetness linger and sweetness adaptation; observations to date support that this hypothesis is correct!
Wood et al. 2011 Review:* “A PAM will exert its effects only when the endogenous agonist is present, resulting in temporal and spatial activity of the endogenous ligand.”
*M. R. Wood, C. Hopkins, J. T. Brogan, P. J. Conn and C. W. Lindsley, Biochemistry2011, 50, 2403-2410. The Coca-Cola Company
What will be the Future of Sweetener Receptor PAMs?
Efficacy of Sweetener Receptor PAMs: Ma et al.,* have reported GPCR PAMs w/ >100-fold enhancements. Can 100-fold enhancers be found for the sweetener receptor?
*L. Ma, M. Seager, M. Wittmann, M. Jacobson, D. Bickel, M. Burno, K. Jones, V. KuzmickGraufelds, G. Xu, M. Pearson, A. McCampbell, R. Gaspar, P. Shughrue, A. Danziger, C. Regan, R. Flick, D. Pascarella, S. Garson, S. Doran, C. Kreatsoulas, L. Veng, C. W. Lindsley, W. Shipe, S. Kuduk, C. Sur, G. Kinney, G. R. Seabrook, W. J. Ray, Proc. Natl. Acad. Sci. USA 2009, 106, 15950-15955.
Agonist Specificity for Sweetener Receptor PAMs: PAMs reported to date exhibit specificity for individual CHO sweeteners. Can PAMs be identified which enhance all sweeteners?
Natural PAMs: PAMs reported to date are synthetic compounds which are being developed as artificial flavors. Can commercially-viable natural enhancers be found which can be labeled as natural flavors?
PAMs for Natural High-Potency Sweeteners: PAMs for stevia sweeteners would enable their use at lower concentrations which may help address their negative taste attributes. Can commercially-viableenhancers for stevia and other natural high-potency sweeteners be found?