Recombinant bacteria for production of indole-3-acetic acid (iaa) and uses thereof
AssigneeSynlogic Operating Company, Inc.
InventorsNing Li, Jian-Rong Gao, Christopher George Bergeron
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Abstract
The present disclosure provides recombinant bacteria for production of indole-3-acetic acid (IAA). Pharmaceutical compositions and methods of treating diseases are also included.
Claims26
A recombinant bacterium comprising one or more gene cassettes for producing indole 3-acetic acid (IAA), wherein a first gene cassette comprises one or more gene sequences encoding a protein selected from the group consisting of TrpE, TrpB, TrpC, TrpD, TrpA, and a combination thereof, and
- wherein the one or more gene cassettes are operably linked to a directly or indirectly inducible promoter that is not associated with the one or more gene sequences and is induced by exogenous environmental conditions.
The bacterium of any one of the previous claims, further comprising a second gene cassette, wherein the second gene cassette comprises one or more sequences encoding a protein selected from the group consisting of AroG, TrpDH, IpdC, Iad1, and a combination thereof.
The bacterium of claim any one of the previous claims, wherein the bacterium further comprises a deletion or a mutation in a gene encoding tryptophan transcriptional repressor (TrpR) and/or a deletion or a mutation in a gene encoding tryptophanase (TnaA).
The bacterium of any one of the previous claims, wherein the promoter is directly or indirectly induced by low-oxygen or anaerobic conditions.
The bacterium of any one of the previous claims, wherein the promoter is an FNR-inducible promoter.
The bacterium of any one of the previous claims, wherein the one or more gene cassettes and operatively linked promoter are present on a plasmid in the bacterium.
The bacterium of any one of the previous claims, wherein the bacterium is a non-pathogenic bacterium.
The bacterium of any one of the previous claims, wherein the bacterium is a probiotic or a commensal bacterium.
The bacterium of claim any one of the previous claims, wherein the bacterium is selected from the group consisting of Bacteroides, Bifidobacterium, Clostridium, Escherichia, Lactobacillus, and Lactococcus.
The bacterium of any one of the previous claims, wherein the bacterium is capable of producing about 1 μM IAA to about 200 μM IAA.
The bacterium of any one of the previous claims, wherein the bacterium is capable of producing about 1 μM IAA to about 200 μM tryptophan.
A recombinant bacterium comprising
- one or more gene cassettes for producing indole 3-acetic acid (IAA), wherein a first gene cassette comprises one or more gene sequences encoding a protein selected from the group consisting of TrpE, TrpB, TrpC, TrpD, TrpA, and a combination thereof;
- and a second gene cassette, wherein the second gene cassette comprises one or more sequences encoding a protein selected from the group consisting of AroG, TrpDH, IpdC, Iad1, and a combination thereof;
- and
- wherein the one or more gene cassettes are operably linked to a directly or indirectly inducible promoter that is not associated with the one or more gene sequences and is induced by exogenous environmental conditions.
A pharmaceutically acceptable composition comprising the bacterium of any one of the previous claims and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.