培養装置の開発とその実用的利用

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The traditional method of designing and scaling up bioreactors for aerobic microorganisms has been based mainly on quantitative indices of the oxygen supplied to the inoculated microorganisms. However, many experiments based on such oxygen indices have produced unsatisfactory results. The author and his group have developed new bioreactors which take account not only of the oxygen uptake capacity but of the whole range of cell properties. Here, the author summarizes the group's work on the following four new bioreactors and outlines their practical application. 1. In response to the two problems of adequate oxygen supply and hydrodynamic stress associated with oxygen supply by aeration-agitation, a new rotating drum fermentor and a new jar fermentor with a modified paddle-type impeller were developed for culturing plant cells at high density. Industrial-scale (1kl) production of shikonin derivatives through cultivation of Lithospermum erythrorhizon cells at high density was achieved for the first time in both of these bioreactors. 2. In response to the two problems of oxygen supply and efficient mixing, the Maxblend fermentor equipped with the Maxblend impeller and a spiral sparger was developed for high-viscosity fermentation broth. Industrial-scale (10kl) production of hyaluronic acid from Streptococcus zooepidemicus cells in high-viscosity fermentation broth was achieved using this fermentor. 3. A special pressure-proof fermentor with pressure control system was used to study the effects on microorganisms in large fermentors of (a) liquid pressure gradient between liquid surface layer and liquid bottom layer, and (b) dissolved gas gradient. The scale-up of bialaphos production from a 3l jar fermentor to a 300kl industrial fermentor was achieved using a new scale-up method based on the results obtained with the special pressure-proof fermentor. 4. A new system (apparatus) for real-time quantitative assessment of individual cell activities in a mixed culture system was developed. The system was used to analyze individual cell growth activities in mixed culture systems of two or three strains.
2006-01-25

培養装置の開発とその実用的利用

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