METHODS FOR CONTROLLING FERMENTATION FEED RATES
The present disclosure relates to methods for enhancing productivity or yield in fermentation. The methods provide monitoring one or more compounds produced by culture cells as a feedback control for the feed rate of the fermentation.
1 . A method for providing sugar to a microbial culture comprising the steps of:
a. feeding sugar to a microbial culture growing in fermentation medium at an initial rate;
b. measuring ethanol concentration in off-gas from the fermentation medium;
c. when the ethanol concentration in the off-gas increases, decreasing the sugar feed rate; and
d. when the ethanol concentration in the off-gas decreases, increasing the sugar feed rate.
2 . The method of claim 1 , wherein sugar is fed to the fermentation medium continuously.
3 . The method of claim 1 , wherein the ethanol concentration in the off-gas is measured continuously.
4 . The method of claim 1 , wherein the sugar feed rate is maintained within ±25% of the initial feed rate.
5 . The method of claim 1 , wherein the sugar feed rate is maintained within ±15% of the initial feed rate.
6 . The method of claim 1 , wherein the sugar feed rate is maintained within ±10% of the initial feed rate.
7 . The method of claim 1 , wherein the feed rate is 1 to 25 g/L/hr.
8 . The method of claim 1 , wherein the oxygen uptake rate of the microbial culture is maintained.
9 . The method of claim 1 , wherein the oxygen uptake rate of the microbial culture is maintained by agitation.
10 . The method of claim 1 , wherein the oxygen uptake rate of the microbial culture is 1-150 mmol O 2 /L/hr.
11 . The method of claim 1 , wherein the ethanol concentration in the off-gas is 50-750 ppm.
12 . The method of claim 1 , wherein the ethanol concentration in the off-gas is 100-200 ppm.
13 . The method of claim 1 , wherein the ethanol concentration in the off-gas is 200-300 ppm.
14 . The method of claim 1 , wherein the ethanol concentration in the off-gas is 250-350 ppm.
15 . The method of claim 1 , wherein the ethanol concentration in the off-gas is 550-650 ppm.
16 . The method of claim 1 , that is maintained for 1-10, 2-9, 3-7, or 4-6 days.
17 . The method of claim 1 , wherein the microbial culture is prokaryotic.
18 . The method of claim 1 , wherein the microbial culture is eukaryotic.
19 . The method of claim 1 , wherein the microbial culture is yeast.
20 . The method of claim 1 , wherein the microbial culture is S. cerevisiae.
21 . The method of claim 1 , wherein the microbial culture is recombinant.
22 . The method of claim 1 , wherein the microbial culture produces a water-immiscible compound.
23 . The method of claim 1 , wherein the microbial culture produces an isoprenoid, polyketide, or fatty acid.
24 . The method of claim 1 , wherein the microbial culture produces a sesquiterpene.