Mycophenolic acid (MPA) 具有抗牛皮癬、抗真菌、抗細菌及抗病毒的能力，且已被證實為Inositol MonoPhosphate DeHydrogenase (IMPDH) 之非競爭型免疫抑制劑，針對淋巴細胞之合成路徑進行抑制而達到降低免疫反應的發生，因此在臨床上被用來預防器官移植所產生的排斥現象。實驗上利用微生物Penicillium brevicompactum進行深層液態發酵 (submerged fermentation) 來生產MPA。 本研究探討添加有機酸對P. brevicompactum生長及生產MPA的影響，其中發現於三羧酸循環中所代謝之有機酸如檸檬酸及琥珀酸能影響P. brevicompactum生長及產物代謝。在添加檸檬酸的情況下能促進菌體生長及加速碳源的消耗，提升菌體比生長速率 (μ) ，可達0.0189，為控制組的1.56倍，且能縮短發酵所需時間約25 hr，產率 (productivity) 提升為控制組的1.3倍；而添加琥珀酸則能提高MPA的產量及提升單位菌體對產物的轉化率 (Yp/x) ，以添加1 g/L達最高MPA產量0.536 g/L，約提升為控制組的1.27倍，單位菌體對產物的轉化率為60.06 mg/g，約為控制組1.33倍。 Mycophenolic acid (MPA) has been to be antipsoriasis, antifungal, antibacterial and antiviral. It was demonstrated that MPA is a non-competitive immunosuppressive agent for Inositol MonoPhosphate DeHydrogenase (IMPDH) by inhibiting de novo purine biosynthesis of lymphocytes. Therefore, MPA is used clinically to prevent rejection of transplanted organs. In this study, Penicillium brevicompactum was used to product MPA in submerged fermentation. Effects of various organic acids on cell growth and production of a useful bioactive metabolite, MPA, by submerged cultivation of Penicillium brevicompactum were investigated. The organic acid such as citric acid and succinic acid, which present in the tricarboxylic acid cycle, were found to affect the cell growth and its metabolism. Addition of citric acid stimulated cell growth, increased consumption rate of carbon source and reduced fermentation time about 25 hr.The specific growth rate and productivity were 1.56 and 1.3 times than that of control-level, respectively. In addition, addition of succinic acid under 1 g/L concentration increased MPA production to 0.536 g/L, which was 1.27 times than that of control-level. Meanwhile the Yp/x increased 1.33 times than that of control-level.
