HIGH pH METHODS AND COMPOSITIONS FOR CULTURING GENETICALLY MODIFIED HOST CELLS
The present disclosure relates to the methods and compositions for enhancing productivity or yield in fermentation. The methods and compositions provide culturing host cells at a high pH and compositions for culturing host cells at a high pH.
1 . A method for culturing genetically modified host cells, comprising the steps of:
a. providing a population of genetically modified host cells; and
b. culturing the population in a culture medium at a pH selected from 5.1-7.0.
2 . The method of claim 1 , wherein the pH is selected from 5.3-6.0.
3 . The method of claim 1 , wherein the pH is about 5.3.
4 . The method of claim 1 , wherein the pH is about 5.5.
5 . The method of claim 1 , wherein the pH is about 6.0.
6 . The method of any of the previous claims , wherein the genetically modified host cells are yeast cells.
7 . The method of any of the previous claims , wherein the genetically modified host cells are S. cerevisiae cells.
8 . The method of any of the previous claims , wherein the genetically modified host cells are capable of producing one or more heterologous non-catabolic compounds.
9 . The method of claim 7 , wherein the genetically modified host cells are capable of producing a human milk oligosaccharide.
10 . The method of claim 8 , wherein the genetically modified host cells are capable of producing 2′-fucosyllactose.
11 . The method of any of the previous claims , wherein the genetically modified host cells are capable of producing a nitrogenous substance.
12 . The method of claim 11 , wherein the genetically modified host cells are capable of producing riboflavin.
13 . The method of any of the previous claims wherein culturing at the pH is maintained for at least 1-10, 2-9, 3-7, or 4-6 days.
14 . The method of any of the previous claims wherein culturing at the pH is maintained for 1-10 days.
15 . The method of any of the previous claims wherein productivity is increased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
16 . The method of any of the previous claims wherein yield is increased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
17 . The method of any of the previous claims wherein biomass is increased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
18 . The method of any of the previous claims wherein cell density is increased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
19 . The method of any of the previous claims wherein host cell health is increased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
20 . The method of any of the previous claims wherein ATP consumption is decreased by at least 1%, 5%, 10%, 15%, or 20%, compared to the same cell strain grown under conventional conditions.
21 . A heterologous non-catabolic compound produced by the methods of any of the previous claims .
22 . The heterologous non-catabolic compound of claim 21 that is a human milk oligosaccharide.
23 . The heterologous non-catabolic compound of claim 21 that is 2′-fucosyllactose.
24 . The heterologous non-catabolic compound of claim 21 that is a nitrogenous substance.
25 . The heterologous non-catabolic compound of claim 21 that is riboflavin.