Fluorosensor controlled fed-batch production of cyclosporine

C - Chemistry – Metallurgy – 12 – P

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Details

C12P 21/04 (2006.01) C12N 1/14 (2006.01) C12N 1/20 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2102132

TITLE Fluorosensor Controlled Fed-Batch Production of Cyclosporine ABSTRACT Improvements are disclosed in relation to fed-batch cyclosporine production, including a nutrient medium useful therein, having a C:N ratio in the range of about 11:1, and comprising: from 15 to 30 g/L of fructose; and, a N source which reduces pH as it is metabolized. In addition, a fed- batch fermentation process for production of cyclosporine includes generating an NADH-flourescence signal in response to monitored cyclosporine-producing B. nivea NAD/NADH oxidation states during carbohydrate substrate fermentation. That signal is correlated against a predetermined carbohydrate utilization profile for said B. nivea under predetermined fermentation conditions, and metered fed-batch carbohydrate supplement is added to the fermentation in response to changes in the signal that are representative of a drop in carbohydrate concentration to a predetermined level.

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