Clavulanic acid是由Streptomyces clavuligerus發酵生產的β-lactamase抑制劑，clavulanic acid與amoxicillin的合併使用在醫療上是成功的藥方。本論文利用批式與進料批式的操作，以S. clavuligerus進行clavulanic acid的發酵生產，探討ammonium ion在培養過程中所扮演的角色、前驅物ornithine、arginine對生化合成的影響及尋求發酵槽最適操作參數。在搖瓶培養過程中，ammonium ion對菌體生長有促進效果但對clavulanic acid生化合成卻有明顯的抑制現象，ornithine或arginine搭配甘油批式進料培養中，ornithine進料對clavulanic acid生化合成的促進效果表現較佳。發酵槽批式培養操作參數探討所得最佳操作條件為攪拌速率700 rpm及通氣流量 2 l/min，利用發酵槽將甘油濃度控制在1~4 g/l及ornithine進料，所生成之clavulanic acid濃度可達525 mg/l，為批式培養的1.25倍。

Clavulanic acid is one of the fermentation products through secondary metabolism by Streptomyces clavuligerus. It is also a specific and irreversible inhibitor of a wide range of bacterial β-lactamase. The combination of clavulanic acid and amoxicillin has been used in human therapy extensively. The purpose of this study is to investigate the role of ammonium ion in the ferment culture, to explore the effect of precursors on the biosynthesis of clavulanic acid using S. clauvligerus in fed-batch fermentations and to seek out the optimal values of the parameters of the fermenter operation. A regularly intermittent feeding of ammonium ion improved the growth rate of S. clauvligerus but the biosynthesis of clavulanic acid was inhibited. The result of intermittent feeding of ornithine and glycerol in terms of maximum production of clavulanic acid was better than that of feeding of arginine and glycerol. The optimum operation condition of fermenter culture was 700 rpm of agitation rate and 2 l/min of aeration rate. In fermenter culture, the controlling glycerol concentration between 1~4 g/l and coupling with intermittent feeding of ornithine resulted in a maximum production of clauvlanic acid of 525 mg/l, which was 1.25 times that obtained in batch culture.

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