蛹虫草菌深层液体发酵耦合大孔树脂吸附高效生产虫草素

关海晴; 李鸿宇; 李倩; 刘冰南; 王际辉; 王亮

doi:10.11949/0438-1157.20190076

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蛹虫草菌深层液体发酵耦合大孔树脂吸附高效生产虫草素

生物化学工程与技术 | 更新时间：2026-07-24

- 蛹虫草菌深层液体发酵耦合大孔树脂吸附高效生产虫草素
- Efficient production of cordycepin during submerged liquid fermentation by Cordyceps militaris coupled with macroporous resin adsorption
- 化工学报 2019年70卷第7期页码：2675-2683
- 作者机构：
  
  1.大连工业大学生物工程学院，辽宁大连 116034
  2.大连大学生命科学与技术学院，辽宁大连 116622
  3.东莞理工学院化学工程与能源技术学院，广东东莞 523808
- 作者简介：
  
  关海晴（1994—），女，硕士研究生，1446757116@qq.com
  王际辉（1969—），男，博士，教授，wangjh@dlpu.edu.cn
  王亮(1986—)，男，博士，讲师，wangliang@dlpu.edu.cn
- 基金信息：
  
  国家重点研发计划项目(2018YFC1406800);国家自然科学基金项目(31500040);辽宁省科技厅自然科学基金计划重点项目(20170520102)
- DOI：10.11949/0438-1157.20190076
  中图分类号： Q 815
- 收稿：2019-01-25，
  
  修回：2019-04-17，
  
  网络首发：2026-07-24，
  
  纸质出版：2019-07-05
- 稿件说明：
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关海晴, 李鸿宇, 李倩, 刘冰南, 王际辉, 王亮. 蛹虫草菌深层液体发酵耦合大孔树脂吸附高效生产虫草素[J]. 化工学报, 2019, 70(7): 2675-2683

GUAN Haiqing, LI Hongyu, LI Qian, LIU Bingnan, WANG Jihui, WANG Liang. Efficient production of cordycepin during submerged liquid fermentation by Cordyceps militaris coupled with macroporous resin adsorption[J]. CIESC Journal, 2019, 70(7): 2675-2683
关海晴, 李鸿宇, 李倩, 刘冰南, 王际辉, 王亮. 蛹虫草菌深层液体发酵耦合大孔树脂吸附高效生产虫草素[J]. 化工学报, 2019, 70(7): 2675-2683 DOI： 10.11949/0438-1157.20190076.

GUAN Haiqing, LI Hongyu, LI Qian, LIU Bingnan, WANG Jihui, WANG Liang. Efficient production of cordycepin during submerged liquid fermentation by Cordyceps militaris coupled with macroporous resin adsorption[J]. CIESC Journal, 2019, 70(7): 2675-2683 DOI： 10.11949/0438-1157.20190076.

摘要

虫草素是一种核苷类抗生素，具有抗癌、抗肿瘤等活性，主要由蛹虫草菌液体发酵生产，然而低产量限制了其应用。考虑到高浓度虫草素积累对其生物合成过程产生强烈反馈抑制，提出了应用发酵分离耦合技术移除部分虫草素、弱化反馈抑制作用以提高虫草素产量的策略。通过静态吸附实验，筛选出虫草素吸附和解吸性能良好的大孔树脂NKA-Ⅱ，并优化了大孔树脂使用量（60 g·L

-1

）、吸附温度（37℃）和解吸剂种类（100%乙醇）。在30 g·L

-1

葡萄糖的分批发酵体系中，经过两次树脂吸附，发酵21 d后虫草素产量达到644.50 mg·L

-1

，较对照组提高32.07%；随后，将树脂吸附分离策略应用于补料分批发酵体系，虫草素产量达到787.50 mg·L

-1

，较对照组提高35.78%。这些结果表明，将虫草素液体发酵与大孔树脂吸附分离耦合，有效弱化了虫草素反馈抑制，显著提高虫草素产量，为虫草素高效生产分离提供了新思路。

Abstract

Cordycepin

as a kind of nucleoside antibiotic

has various biological and pharmaceutical activities

such as anti-cancer and anti-tumor activities. Cordycepin is mainly obtained from liquid culture of

Cordyceps militaris

whose low yield restricted its further application though. Considering the high concentration of cordycepin accumulation to produce strong feedback inhibition on its biosynthesis process

a strategy to remove some cordycepin and weaken the feedback inhibition to increase the production of cordycepin by fermentation separation coupling technique was proposed. Next

static adsorption test was taken and macroporous resin NKA-II was screened

followed by optimization of adsorption conditions such as resin usage (60 g·L

-1

)

temperature (37℃)

and desorption solvent (100% ethanol)

giving 644.50 mg·L

-1

cordycepin in fermentation under 30 g·L

-1

initial glucose with repeated adsorption processing (twice)

32.07% higher than the control. To further improve the cordycepin yield

fed-batch fermentation coupled with resin adsorption separation was performed

giving a final yield of 787.50 mg·L

-1

which was 35.78% higher than the control. It was found that the strategy of submerged liquid fermentation coupled with macroporous resin adsorption could efficiently weaken the feedback inhibition of cordycepin

and dramatically enhance the productivity of product

providing novel ideas for industrial cordycepin production.

关键词

Keywords

references

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