# US 12,215,310 B2 · Means and methods to modulate probiotic potency of the yeast Saccharomyces boulardii

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- Number: US 12,215,310 B2
- Document ID: US12215310B2
- Status: Granted
- Kind: B2
- Application number: 16/646,936
- Filed: 2018-09-14
- Published: 2020-08-27
- Granted: 2025-02-04
- Earliest claimed: 2017-09-15
- Assignees: Vib Vzw; Katholieke Universiteit Leuven
- Applicants: Vib Vzw; Katholieke Universiteit Leuven, K.U.Leuven R&D
- Inventors: Johan Thevelein; Benjamin Offei; Maria Remedios Foulquié Moreno; Paul Vandecruys
- Web page: https://patentgrep.com/patent/US12215310B2

## CPC

- C12N 1/18: Baker's yeast; Brewer's yeast
- A23L 33/14: Yeasts or derivatives thereof
- A61K 36/064: Saccharomycetales, e.g. baker's yeast
- C07K 14/395: from Saccharomyces
- C12N 1/185: Saccharomyces isolates
- C12P 7/54: Acetic acid (vinegar C12J)
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- C12R 2001/865: Saccharomyces cerevisiae
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- C12R: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS

## Abstract

Described herein are probiotics, more particularly [to] the probiotic yeast Saccharomyces boulardii. Even more particularly described herein are enhanced probiotic potency S. boulardii. Also described here are mutant alleles useful to develop yeast strains with enhanced production of acetic acid. In addition, described here is the use of such yeast strains for the production of dietary supplements or pharmaceutical compositions to improve gastrointestinal comfort.

## Claims

### Claim 1

A Saccharomyces boulardii strain comprising a homozygous or hemizygous mutant WHI2 allele,
wherein the mutant allele completely abolishes Whi2 function,
wherein the wild type allele of Whi2 is SEQ ID NO: 3,
wherein the mutant allele
has been disrupted or deleted by homologous recombination or disrupted with a nuclease, and
wherein the strain produces, at 37° C., a cell-free supernatant with a pH lower than 5.

### Claim 2 (depends on 1)

The Saccharomyces boulardii strain of claim 1, wherein the acidification of the supernatant results from the production of acetic acid by the Saccharomyces boulardii strain.

### Claim 3 (depends on 1)

The Saccharomyces boulardii strain of claim 1, wherein the strain is growth deficient on acetic acid.

### Claim 4 (depends on 1)

A dietary supplement or pharmaceutical composition comprising the Saccharomyces boulardii strain of claim 1.

### Claim 5 (depends on 1)

A method of treating of gastrointestinal disorders in a mammal, the method comprising administering to the mammal a dietary supplement or pharmaceutical composition comprising a therapeutically effective amount of the Saccharomyces boulardii strain of claim 1.

### Claim 6 (depends on 1)

The Saccharomyces boulardii strain of claim 1, wherein the WHI2 allele comprises SEQ ID NO:1.

### Claim 7

A Saccharomyces boulardii strain comprising a heterologous WHI2 allele, wherein the allele completely abolishes Whi2 function.