Methods and compositions for methionine restriction
AssigneePetri Bio, Inc.
InventorsJoseph SCHINAMAN, Shu LI
Life of this patent
Estimating the term…
Abstract
The technology described herein is directed to compositions and methods for reducing levels of methionine. In various aspects described herein are: engineered methionine-reducing probiotic microorganisms; engineered methanethiol-reducing probiotic microorganisms; and engineered taurine-producing probiotic microorganisms. Also described herein are methods of using such engineered microorganisms, such as for reduction of bioavailable methionine or for treatment of a methionine-associated disease or disorder. Also described herein are probiotic dietary supplements, pharmaceutical compositions, and food compositions comprising such engineered microorganisms.
Claims63
An engineered probiotic microorganism for reducing bioavailable methionine levels, comprising:
- a) at least one exogenous copy of at least one gene encoding an enzyme that catalyzes the degradation of methionine, wherein the gene encoding an enzyme that catalyzes the degradation of methionine encodes a methionine gamma lyase.
An engineered probiotic microorganism for reducing bioavailable methionine levels, comprising:
- a) at least one exogenous copy of at least one gene encoding an enzyme that catalyzes the degradation of methionine, wherein the gene encoding an enzyme that catalyzes the degradation of methionine encodes a methionine gamma lyase;
- and
- b) at least one of the following:
- i) at least one exogenous copy of at least one functional methionine importer gene;
- and/or
- ii) at least one endogenous methionine importer gene comprising at least one engineered activating modification.
An engineered probiotic microorganism for reducing bioavailable methionine levels, comprising:
- a) at least one exogenous copy of at least one gene encoding an enzyme that catalyzes the degradation of methionine;
- b) at least one exogenous copy of at least one functional methionine importer gene;
- c) at least one endogenous methionine importer gene comprising at least one engineered activating modification;
- d) at least one endogenous methionine synthesis gene comprising at least one engineered inactivating modification;
- e) at least one endogenous methionine regulator gene comprising at least one engineered inactivating or activating modification;
- or
- f) a combination of two or more of (a)-(e).
An engineered probiotic microorganism for reducing bioavailable methionine levels, the microorganism comprising:
- a) at least one endogenous methionine synthesis gene comprising at least one engineered inactivating modification;
- b) at least one copy of an exogenous gene encoding a homocysteine methyltransferase enzyme;
- c) at least one copy of an exogenous gene encoding a sulfinoalanine decarboxylase enzyme;
- and
- d) at least one copy of an exogenous gene encoding a Flavin-containing monooxygenase (FMO) enzyme;
- wherein the engineered probiotic microorganism expresses endogenously or exogenously encoded cystathionine β-synthase, cystathionine gamma lyase and cysteine dioxygenase enzymes.
An engineered probiotic microorganism for reducing bioavailable methionine levels, the microorganism comprising:
- a) at least one endogenous methionine synthesis gene comprising at least one engineered inactivating modification;
- b) at least one copy of an exogenous gene encoding a glycine N-methyltransferase (GNMT) enzyme;
- c) at least one copy of an exogenous gene encoding a sarcosine N-methyl transferase (SNMT) enzyme;
- d) at least one copy of an exogenous gene encoding a sulfinoalanine decarboxylase enzyme;
- and
- e) at least one copy of an exogenous gene encoding a Flavin-containing monooxygenase (FMO) enzyme;
- wherein the engineered probiotic microorganism expresses endogenously or exogenously encoded methionine adenosyl transferase (MetK), adenosylhomocysteinase (ahcY), cystathionine β-synthase, cystathionine gamma lyase and cysteine dioxygenase enzymes.
A method of reducing a level of methanethiol, the method comprising contacting methanethiol with a probiotic microorganism that encodes and expresses an exogenous gene encoding a methanethiol catabolizing enzyme.
A method of reducing odor produced by a population of gut microbiota that produced methanethiol, the method comprising introducing an engineered probiotic microorganism to the gut microbiota, wherein the engineered probiotic microorganism encodes and expresses an exogenous gene encoding a methanethiol catabolizing enzyme.
The method of claim 63, wherein the microorganism is introduced via oral administration.
Dependencies are inferred from the claim text.