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US 2019/0071680 A1Published application
Microbial production of nicotinic acid riboside
AssigneeDsm IP Assets B.V.
InventorsAdam G. LAWRENCE, Celine VIAROUGE
Life of this patent
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Abstract
The present invention relates to a novel method, expression vectors, and host cells for producing nicotinic acid riboside by regulating the pathways that lead to the production of nicotinic acid riboside.
Claims16
1-19. (canceled)
A genetically modified bacterium capable of producing nicotinic acid riboside (NaR), wherein the bacterium comprises at least one modification selected from a group consisting of:
- a) blocking or reducing the activity of a protein which functions to repress NAD+ biosynthesis by repressing transcription of nadA, nadB, nadC genes or combinations thereof;
- b) adding or increasing the transcription of a gene which encodes L-aspartate oxidase, quinolate synthase, quinolate phoshoribosyltransferase, or combinations thereof;
- and
- c) blocking or reducing the activity of a protein which functions as a nicotinic acid mononucleotide adenyltransferase;
- wherein the bacterium with said at least one modification produces an increased amount of NaR than the bacterium without any of said modifications;
- and
- further comprising one or more additional modifications selected from the group consisting of:
- d) blocking or reducing the activity of a protein which functions as a nicotinic acid riboside phosphorylase;
- e) blocking or reducing the activity of a protein which functions as a nicotinic acid riboside kinase;
- f) blocking or reducing the activity of a protein which functions as a nicotinic acid riboside transport protein;
- g) blocking or reducing the activity of a protein which functions as a nicotinic acid phosphoribosyl transferase;
- h) adding or increasing the activity of a protein which functions as a nicotinamide mononucleotide amidohydrolase;
- and
- i) adding or increasing the activity of a protein which functions as a nicotinic acid mononucleotide hydrolase.
11 more elements
The bacterium of claim 1, wherein said bacterium is selected from a group consisting of:
- E. coli, B. subtilis, C. glutamicum, A. baylyi and R. eutropha.
A method for producing NaR, comprising:
- culturing a bacterium cell under conditions effective to produce NaR and recovering NaR from the medium and thereby producing NaR, wherein the host microorganism comprises at least one modification selected from the group consisting of:
- a) blocking or reducing the activity of a protein which functions to repress NAD+ biosynthesis by repressing transcription of nadA, nadB, nadC genes or combinations thereof;
- b) adding or increasing the transcription of a gene which encodes L-aspartate oxidase, quinolate synthase, quinolate phosphoribosyltransferase, or combinations thereof;
- and
- c) blocking or reducing the activity of a protein which functions as a nicotinic acid mononucleotide adenyltransferase.
2 more elements
Dependencies are inferred from the claim text.