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青霉素生產(chǎn)工藝優(yōu)化及代謝分析提高產(chǎn)量

Optimization of the feeding process and metabolism analysis to improve the yield of penicillin

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摘要

青霉素作為第一個(gè)被應(yīng)用的β-內(nèi)酰胺類抗生素，至今仍在醫(yī)療健康領(lǐng)域發(fā)揮著重要作用。在產(chǎn)黃青霉補(bǔ)料分批發(fā)酵的傳統(tǒng)工藝中，青霉素合成速率在100h左右開始快速下降。針對(duì)這一問(wèn)題，本文設(shè)計(jì)了后期倒種和后期補(bǔ)鹽兩種工藝優(yōu)化策略，對(duì)傳統(tǒng)工藝加以改進(jìn)。結(jié)果表明，后期倒種工藝中，發(fā)酵250h后仍具有較高的青霉素合成速率，但后期倒種使大量仍具有較強(qiáng)青霉素合成能力的菌體流失，造成嚴(yán)重浪費(fèi)。后期補(bǔ)鹽工藝中，發(fā)酵終末青霉素總產(chǎn)量以及產(chǎn)物對(duì)糖得率分別較原始工藝提高了28.46%和34.55%。對(duì)細(xì)胞代謝途徑及菌體形態(tài)等的進(jìn)一步探討表明，傳統(tǒng)工藝發(fā)酵后期包括磷源及金屬離子在內(nèi)的痕量營(yíng)養(yǎng)物質(zhì)的不足會(huì)影響菌體的生長(zhǎng)，并且抑制前體氨基酸及NADPH的合成，從而造成了青霉素產(chǎn)率的下降，菌株自身的發(fā)酵效率潛力依舊可以挖掘。

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.

關(guān)鍵詞

產(chǎn)黃青霉 /補(bǔ)料分批發(fā)酵 /工藝優(yōu)化{{custom_keyword}} /

Key words

Process optimization /Fed-batch fermentation /Penicillium chrysogenum{{custom_keyword}} /

李云龍1 唐文俊1 白成海3 黃明志1,2,* 儲(chǔ)炬1,2 莊英萍1,2.青霉素生產(chǎn)工藝優(yōu)化及代謝分析提高產(chǎn)量[J]. 中國(guó)抗生素雜志, 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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