Microbial production of nicotamide riboside
AssigneeDsm IP Assets B.V.
InventorsAdam G. LAWRENCE, Celine ViAROUGE
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to a novel method, expression vectors, and host cells for producing nicotinamide riboside by regulating the pathways that lead to the production of nicotinamide riboside.
Claims26
A genetically modified bacterium capable of producing nicotinamide riboside (NR), wherein the bacterium comprises at least one modification selected from a group consisting of:
- a) adding the activity of a heterologous nicotinic acid amidating protein (NadE*);
- and
- b) adding or increasing the activity of a nicotinamide adenine dinucleotide (NAD+) hydrolyzing protein,
- wherein the bacterium with said at least one modification produces an increased amount of NR than the bacterium without any of said modifications.
A method for producing NR, comprising:
- culturing a bacterium cell under conditions effective to produce NR and recovering NR from the medium and thereby producing NR, wherein the host microorganism comprises at least one modification selected from the group consisting of:
- a) adding the activity of a heterologous heterologous nicotinic acid amidating protein (NadE*);
- b) adding or increasing the activity of a nicotinamide adenine dinucleotide (NAD+) hydrolyzing protein;
- c) 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;
- d) blocking or reducing the activity of a protein which functions as a nicotinamide riboside transporter protein;
- e) blocking or reducing the activity of a protein which functions as a nicotinic acid mononucleotide adenyltransferase;
- f) blocking or reducing the activity of a protein which functions as a nicotinamide mononucleotide amidohydrolase;
- g) blocking or reducing the activity of a protein with function as a purine nucleoside phosphorylase;
- h) adding or increasing the activity of a protein which functions as a nicotinamide mononucleotide hydrolase;
- and
- i) adding or increasing the activity of a protein which functions as a L-aspartate oxidase, a quinolate synthase, a quinolate phoshoribosyltransferase, or combinations thereof.
A method for producing NR, comprising:
- culturing a bacterium cell under conditions effective to produce NR and recovering NR from the medium and thereby producing NR, wherein the host microorganism comprises at least one modification selected from the group consisting of:
- a) adding the activity of a heterologous nicotinic acid amidating protein (NadE*);
- and
- b) adding or increasing the activity of a nicotinamide adenine dinucleotide (NAD+) hydrolyzing protein.
A genetically modified bacterium wherein as a result of the genetic modification, the bacterium produces NR and can accumulate the produced NR to at least 100 mg/L in the fermentation broth in which the bacterium is grown.
Dependencies are inferred from the claim text.