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Use of Model-Based Nutrient Feeding for Improved Production of Artemisinin by Hairy Roots of Artemisia Annua in a Modified Stirred Tank Bioreactor

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Abstract

Artemisinin has been indicated to be a potent drug for the cure of malaria. Batch growth and artemisinin production kinetics of hairy root cultures of Artemisia annua were studied under shake flask conditions which resulted in accumulation of 12.49 g/L biomass and 0.27 mg/g artemisinin. Using the kinetic data, a mathematical model was identified to understand and optimize the system behavior. The developed model was then extrapolated to design nutrient feeding strategies during fed-batch cultivation for enhanced production of artemisinin. In one of the fed-batch cultivation, sucrose (37 g/L) feeding was done at a constant feed rate of 0.1 L/day during 10–15 days, which led to improved artemisinin accumulation of 0.77 mg/g. The second strategy of fed-batch hairy root cultivation involved maintenance of pseudo-steady state sucrose concentration (20.8 g/L) during 10–15 days which resulted in artemisinin accumulation of 0.99 mg/g. Fed-batch cultivation (with the maintenance of pseudo-steady state of substrate) of Artemisia annua hairy roots was, thereafter, implemented in bioreactor cultivation, which featured artemisinin accumulation of 1.0 mg/g artemisinin in 16 days of cultivation. This is the highest reported artemisinin yield by hairy root cultivation in a bioreactor.

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Acknowledgments

The authors thankfully acknowledge the supply of elite seed material of A. annua from CIMAP Lucknow. The financial support by Ministry of Human Resource Development, New Delhi (India), for the execution of the above project is gratefully acknowledged by one of the authors (Nivedita Patra).

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  1. Nivedita Patra

    Present address: Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Odisha, 769008, India

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  1. Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, 110016, India

    Nivedita Patra & Ashok K. Srivastava

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Correspondence to Ashok K. Srivastava.

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Patra, N., Srivastava, A.K. Use of Model-Based Nutrient Feeding for Improved Production of Artemisinin by Hairy Roots of Artemisia Annua in a Modified Stirred Tank Bioreactor. Appl Biochem Biotechnol 177, 373–388 (2015). https://doi.org/10.1007/s12010-015-1750-8

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