Abstract
本文係針對青黴菌Penicillium chrysm，以不同的菌體形態，在饋料 批次醱酵系統，探討菌體形態對盤尼西林G生成的影響。 青黴菌的生 長形態大致可分為纖維狀菌絲和菌球兩種 。纖維狀菌絲容易使醱酵液黏 稠，增加大規模醱酵槽動力的消耗及產生溶氧不足等問題， 因此，反應 器對菌球和菌絲醱酵的影響，及固定化菌體在生產盤尼西林上的表現常被 討論 。回顧歷來文獻，青黴菌的菌體形態對其生產盤尼西林能力的影響 ，至今仍無明確的定論 。本研究以一饋料批次醱酵系統，在溶氧並無受 限的條件下 ( 飽和溶氧值50 %以上 )， 觀察不同的青黴菌菌體形態在生 產盤尼西林G的結果中發現，以菌絲態生長的菌體會有較快的生長速率， 而以菌球態生長的菌體會有較高的盤尼西林產量。若我們能提供菌體充足 的溶氧，在10小時內的醱酵時間內，菌絲即有1.0 g/的盤尼西林濃度 和0.085 g的比生產量。菌球的系統可在15小時的醱酵時間內，有1.3 g/ 盤尼西林G的濃度，且最高可達到0.1 3 g/的比生產量，菌球雖有較高的 產量，但菌絲生長快速的特性卻可比菌球縮短醱酵時間 20小時左右。但 在提高饋料的葡萄糖濃度後，菌絲可在12小時達到2.0 g/的盤尼西林產量 ，但菌球在此操作條件下，卻只有0.45 g/。由以上的結果發現，對菌絲 而言略嫌不足的葡萄糖量，卻已可滿足菌球的需求，同樣地，高糖濃度的 進料組成使菌絲有更高的盤尼西林產量，但卻使菌球降低了生成能力。因 此，不論何種菌體形態，在醱酵生產盤尼西林時，若供給過量的碳源將使 菌體繼續生長，而不利於盤尼西林的代謝生產。在實際應用上，若溶氧的 問題能解決，以菌絲態醱酵能縮短醱酵時間，可接受高濃度的饋料，比之 菌球形態較有利於盤尼西林的生產。因此，菌體形態對醱酵操作上的確有 非常大的影響。 This research discusses the effect of macroscopic morphology of Penicillium chrysogenum on the production of penicillin in fedbatch culture. Morphology of P. chrysogenum can be categorized into two forms : filamentous mycelium and pellet. Growth under filamentous form will make the broth viscous, in which causes some problem such as more energy consumption and lower oxygen transfer. Consequently, effects of reactor configuration on pellet or filamentous fermentation and immobilization of cells for penicillin production are always investigated. However, the effect of morphology on production of penicillin is still under debate. In the present study, fedbatch fermentation was employed with providing sufficient D. O. ( above 50 % saturated D.O. ) which would not suppress the supply of oxygen for cultivation of P. chrysogenum in both filamentous and pellet forms for production of penicillin G. The results showed that filamentous form grew faster but pellet form had a higher yield. By providing a sufficient amount of D.O., cultivation of P. chrysogenum in the form of filamentous could reach a pen-G concentration of 1.0 g/L or 0.085 gram of penicillin produced per gram of dry cell weight ( g/g ) in 100 hrs. In the form of pellet, the maximum production reached 1.3 g/L or 0.13 g/g in 150 hrs. Although pellet form had a high yield, filamentous form grew faster, which shortened the fermentation time up to 20 hrs. The experimental results showed that feeding on high glucose concentration could reach higher penicillin production in filamentous fermentation, but depress the penicillin production in pellet form. Thus providing excess carbon source in penicillin fermentation, for both cell morphological forms, is a disadvantage to penicillin synthesis. In practical use, if the problem of D.O. could be solved, cultivation of P. chrysogenum in the form of filamentous for penicillin G production would be better than in pellet form because the fermentation time is short and high glucose feeding strategy is suitable. In addition, the morphology of P. chrysogenum would not be a major issue in the production of penicillin if the oxygen transfer is not a problem during the period of cultivation. Hence, the effect of morphology on the production of penicillin is mainly based on engineering manipulation.