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Highly efficient synthesis of boldenone from androst-4-ene-3,17-dione by Arthrobacter simplex and Pichia pastoris ordered biotransformation

  • Rui Tang
  • Yanbing ShenEmail author
  • Min WangEmail author
  • Haijie Zhou
  • Yunqiu Zhao
Research Paper
  • 19 Downloads

Abstract

Boldenone (BD) is an important steroid hormone drug which is the derivative of testosterone. In this study, an ordered biotransformation method was proposed employing Arthrobacter simplex and recombinant Pichia pastoris with 17β-hydroxysteroid dehydrogenase from Saccharomyces cerevisiae to produce BD from androst-4-ene-3,17-dione (AD) efficiently. To lower the oxidation towards BD in A. simplex, the transformation was conducted sequentially by C1,2 dehydrogenation in A. simplex and 17β-carbonyl reduction in recombinant P. pastoris GS115. Moreover, the reaction system was inactivated before recombinant P. pastoris GS115 was added to further inhibit the oxidation of BD by A. simplex, and the productivity of BD was improved 10.6% compared with the control. Furthermore, by optimizing the conditions of transformation from AD to BD, 4.2 g/L BD was generated with 83% productivity from 5.0 g/L AD, which was the highest productivity reported by biological method. This study offers a promising method to produce BD by ordered biotransformation system, which can also be used to manufacture other steroidal compounds that are difficult to acquire directly.

Keywords

Ordered biotransformation Steroid Boldenone Arthrobacter simplex Pichia pastoris 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (21276196 and 21406167), Tianjin Municipal Science and Technology Commission (17PTGCCX00190), the Innovative Research Team of Tianjin Municipal Education Commision (TD13-5013), and Tianjin Municipal Science and Technology Commission (16JCQNJC09100).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, College of BiotechnologyTianjin University of Science and TechnologyTianjinPeople’s Republic of China

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