Gene expression system for probiotic microorganisms
AssigneeZBiotics Company
InventorZachary D. Abbott
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Abstract
Provided herein are recombinant microorganisms that express a subject polypeptide. Microorganisms can comprise an expression construct comprising a flagellin promoter operatively linked with a heterologous nucleotide sequence encoding the subject polypeptide. The flagellin promoter sequence can comprise a genetic modification that reduces CsrA inhibition of translation. Microorganisms also can comprise a genetic modification that reduces FlgM inhibition of SigD initiation of transcription. The target polypeptide can be an aldehyde dehydrogenase. Such microorganisms are useful in the treatment of alcohol hangover.
Claims19
A method for preventing or treating an alcohol hangover, comprising administering to the gut of a subject in need thereof an effective amount of a composition comprising a recombinant bacterium recombinantly engineered to comprise an integrated heterologous nucleotide sequence encoding an aldehyde dehydrogenase, wherein the recombinant bacterium comprises:
- a) a polynucleotide comprising an expression construct comprising a flagellin gene promoter operatively linked with the heterologous nucleotide sequence encoding the aldehyde dehydrogenase, wherein the flagellin gene promoter is an endogenous promoter of the bacterium and is engineered to comprise one or more genetic modifications that reduce Carbon storage regulator A (CsrA) repression of translation of an mRNA transcribed from the flagellin gene promoter;
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- b) a genetic modification of a sigma factor repressor, wherein the modification reduces inhibition of sigma factor initiation of transcription from the flagellin gene promoter.
Dependencies are inferred from the claim text.