Study on the Pilot-Scale Technology of Ginkgolide B Synthesis by Coprinus comatus

Abstract

Ginkgo biloba extract (EGB) has been approved by the Food and Drug Administration in the United States for clinical studies on memory disorders. Ginkgolide B (GB) is the major terpene lactone component of EGB and is a specific and potent antagonist of platelet-activating factor (PAF). In a previous study, we reported the medium composition for the conversion of ginkgolides to GB by Coprinus comatus. In the present study, we applied the response surface methodology (RSM) to optimize the conversion conditions in a 20 L fermenter and applied HPLC-MS/MS, circular dichroism (CD) and infrared (IR) spectroscopy analyses, and nuclear magnetic resonance (NMR) to further confirm the sample structure. The optimal conversion conditions consisted of 12.7 L/min of ventilation, a 156 h conversion time, a 132 rpm rotating speed, a 0.04 MPa fermenter pressure, and a 27.8 °C conversion temperature. Under the optimal conditions, the GB conversion rate was 98.62%, and the GB content of the sample was higher than 98%. HPLC-MS/MS, CD, IR, and NMR analyses showed that the molecular formula of the sample was C20H24O10 and the chemical structure of the sample was in good agreement with the standard GB. Our current study lays the groundwork for the industrial production of GB.