青霉素生产工艺优化及代谢分析提高产量
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青霉素生产工艺优化及代谢分析提高产量
Optimization of the feeding process and metabolism analysis to improve the yield of penicillin
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摘要
青霉素作为第一个被应用的β-内酰胺类抗生素，至今仍在医疗健康领域发挥着重要作用。在产黄青霉补料分批发酵的传统工艺中，青霉素合成速率在100h左右开始快速下降。针对这一问题，本文设计了后期倒种和后期补盐两种工艺优化策略，对传统工艺加以改进。结果表明，后期倒种工艺中，发酵250h后仍具有较高的青霉素合成速率，但后期倒种使大量仍具有较强青霉素合成能力的菌体流失，造成严重浪费。后期补盐工艺中，发酵终末青霉素总产量以及产物对糖得率分别较原始工艺提高了28.46%和34.55%。对细胞代谢途径及菌体形态等的进一步探讨表明，传统工艺发酵后期包括磷源及金属离子在内的痕量营养物质的不足会影响菌体的生长，并且抑制前体氨基酸及NADPH的合成，从而造成了青霉素产率的下降，菌株自身的发酵效率潜力依旧可以挖掘。
Abstract
Penicillin is the first β-lactam antibiotic that plays an important role in the fields of medicine and health. The penicillin synthesis rate tends to fall after 100h in the traditional fed-batch cultivation using Penicillium chrysogenum. In this paper, we improved the traditional bioprocess using the intermittent harvest operation and additional feeding during the later phase of fermentation. The results showed that the intermittent harvest operation could keep a high rate of penicillin synthesis till 250h, while it might lose a large amount of biomass with strong penicillin-production ability and cause serious waste production. While performing the additional feeding strategy, final penicillin titer and penicillin yield were 28.46% and 34.55% higher than that of the original strategy. This work on the account of metabolism pathway and morphology of cell showed that one of the major factors that contributed to the declination in penicillin productivity was the lack of enough amount of some nutrients, for instance, phosphorus and metal ions. By the implementation of extra feeding strategy, the fermentation efficiency could be improved.
关键词
产黄青霉 /补料分批发酵 /工艺优化{{custom_keyword}} /
Key words
Process optimization /Fed-batch fermentation /Penicillium chrysogenum{{custom_keyword}} /
李云龙1 唐文俊1 白成海3 黄明志1,2,* 储炬1,2 庄英萍1,2.青霉素生产工艺优化及代谢分析提高产量[J]. 中国抗生素杂志, 2019, 44(6): 679-686
Optimization of the feeding process and metabolism analysis to improve the yield of penicillin[J]. Chinese Journal of Antibiotics, 2019, 44(6): 679-686
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