SBIR-STTR Award

Family of low caloric sweetners—3D structure
Award last edited on: 1/19/22

Sponsored Program
SBIR
Awarding Agency
NIH : NIDCR
Total Award Amount
$548,670
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Joachim L Weikmann

Company Information

XOMA Corporation (AKA: Xoma Ltd)

2200 Powell Street Suite 310
Berkeley, CA 94608
   (510) 204-7200
   smart@xoma.com
   www.xoma.com
Location: Multiple
Congr. District: 12
County: Alameda

Phase I

Contract Number: 1R43DE009063-01
Start Date: 9/25/89    Completed: 3/24/90
Phase I year
1989
Phase I Amount
$48,670
Most low-caloric sweeteners are synthetic organic compounds like saccharine and cyclamate or more recently, biochemicals such as aspartame, a dipeptide. Their taste characteristics are not easily altered or modified. Due to the quantity of material required to elicit a sweet taste sensation, the amount consumed is high enough to warrant caution concerning their use. In addition, the possibility of their conversion during the processing of the food product to other less safe compounds has also slowed their general acceptance. Thaumatins are a class of natural proteins with a sweet taste many thousand fold more intense than sugar. The gene has been cloned and an expression system developed at INGENE. By random mutation, over one hundred altered proteins have been expressed and taste tested. Many characteristics have been identified and scored, such as persistence, after-taste and stability. The structure of the native protein and each of the mutant forms will be determined at Cryschem in order to elucidate the structure-function relations. Mapping the thaumatin domains that influence the perception of sweetness also provides insight into the structure of the sweet taste receptor. Based on these structures, second generation protein sweeteners with specific desirable characteristics can be designed.

Thesaurus Terms:
food, sweetening agents, nutrition, dietary constituents, caloric content, protein structure and function chemical structure--biological activity, dental caries inhibitors, genetics, mutation, mutants, nutrition related control tag, proteins, binding proteins, lectins plant, sensory-perceptual processes, taste chemistry, analytical methods, crystallography, chemistry, analytical methods, x-ray structure analysis, chemistry, analytical methods, x-ray structure analysis, low (small) angle x-ray technique, genetic manipulation, site-directed mutagenesis

Phase II

Contract Number: 2R44DE009063-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
1991
Phase II Amount
$500,000
The thaumatins are a family of plant-derived proteins with a sweet taste many thousand-fold more intense than sugar. XOMA has purified and sequenced the two major plant proteins and in an effort to improve taste quality, has generated more than 100 thaumatin variants. Most of these have been produced in test amounts via a yeast secretion system. Cryschem is solving the three-dimensional structure of plant thaumatin by X-ray analysis. The structures of thaumatin variants having improved taste properties will then be determined with special emphasis placed on understanding conformational features in regions shown by XOMA's taste tests to affect sweet taste. The combination of structural information with quantitative primate taste tests may allow us to design a second generation of protein sweeteners with specific taste and stability characteristics. Economic production of recombinant thaumatin is a major goal of this project. In taste tests by a trained taste panel using existing food products, recombinant thaumatins have been identified which were preferred over the same products sweetened and flavored with plant thaumatin. Our current method of production is by secretion from S. cerevisiae. Several alternative secretion systems are being tested which should make it possible to produce large quantities of purified protein economically.Awardee's statement of the potential commercial applications of the research:Artificial, low-calorie sweeteners have found rapid acceptance and commercial success in most of the industrialized countries of the world. Thaumatin, a natural plant-derived protein sweetener, although approved for use as a food additive in numerous countries, has not gained wide acceptance due in part to stability, taste, and availability problems. We believe that a detailed understanding of both the structure of this interesting protein and those regions affecting taste and flavor character will enable us to design derivatives tasting and behaving even more sucrose-like. The commercial applications of such a product are extensive.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)