STUDY ON MULTI-FED-BATCH CULTURE

多补料分批培养的研究

• 批准号: 60470120
• 负责人: SHIMIZU SHOICHI
• 金额: $ 2.62万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60470120/
• 关键词: multi-fed-batch culture; methylotroph; Streptomyces laurentii; Pseudomonas fluorescens; automatic feeding; high cell mass cultivation; thiostrepton; Iaurentii; 高菌帯濃度流加培養法のコスト; リパーゼ; 排ガスのC【O_2】濃度; 原価計算式

A fed-batch culture where more kinds of nutrient than two are supplied simultaneously is defined as multi-fed-batch culture and theoretical and experimental studies were performed to develop optimization and automation techniques of the multi-substrate feedings. In the multi-fed- batch culture, the fed-substrates are either multiple compounds or natural nutrients (such as corn steep liquor, defatted soy been meal or yeast extract). As the former case, production of serine from glycine was attempted with a methylotroph by supplying both methanol and oxygen gas automatically. Both methanol concentration and dissolved oxygen concentration were kept constant by detector-controller systems, by which a high final concentration fo serine was accomplished.Since no direct detector system is available for the case of natural nutrients, one has to resort to indirect control indices to feed them automatically. Possible indirect indices are pH and CO2 concentration in the exhaust gas. Effective production of thiostrepton by Streptomyces laurentii was achieved with use of pH-stat modal feeding of multi-substrates. Mass production of lipase by Pseudomonas fluorescens was possible with automatic feeding of olive oil whose feed rate was proportional to the CO_2 evolution ate.Economic significance of high cell mass cultivation was evaluated theoretically in terms of both raw material cost and running cost.

将同时补料两种以上的营养物质的分批补料培养称为多底物分批补料培养，并对多底物分批补料的优化和自动化技术进行了理论和实验研究。在多补料分批培养中，补料基质是多种化合物或天然营养物（如玉米浆、脱脂大豆粉或酵母提取物）。作为前一种情况，尝试用甲基营养菌通过自动供应甲醇和氧气来从甘氨酸生产丝氨酸。甲醇浓度和溶解氧浓度通过检测控制系统保持恒定，从而实现丝氨酸的高最终浓度。由于没有直接检测系统可用于天然营养物的情况下，人们不得不求助于间接控制指标来自动进料。可能的间接指标是废气中的pH值和CO2浓度。采用恒pH多底物模式补料，实现了罗伦链霉菌高效生产硫链丝菌素。采用与CO_2释放速率成正比的橄榄油自动补料，使荧光假单胞菌脂肪酶的大规模生产成为可能。从原料成本和运行成本两个方面对高细胞量培养的经济意义进行了理论分析。

项目成果

Takahiro SUZUKI: Applied Microbiology and Biotechnology. 28. 417-422 (1988)

铃木贵宏：应用微生物学和生物技术。

Takahiro SUZUKI: Applied Microbiology and Biotechnology. 25. 526-531 (1987)

铃木贵宏：应用微生物学和生物技术。

Pramote SIRIROTE: "Production of L-serine from methanol and glycine by resting cells of a methylotroph under automatically controlled conditions" Journal of Fermentation Technology. 64. 389-396 (1986)

Pramote SIRIROTE：“在自动控制条件下，甲基营养菌的静息细胞从甲醇和甘氨酸生产 L-丝氨酸”《发酵技术杂志》。

Tsuneo YAMANE: Journal of Fermentation Technology. 66. (1988)

Tsuneo YAMANE：发酵技术杂志。

Takahiro SUZUKI: "Mass production of lipase by fed-batch culture of Pseudomonas fluorescens" Applied Microbiology and Biotechnology. 28. 417-422 (1988)

Takahiro SUZUKI：“通过补料分批培养荧光假单胞菌大规模生产脂肪酶”应用微生物学和生物技术。