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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Key Laboratory of Industrial Fermentation Microbiology (Tian** University of Science and Technology), Ministry of Education, Tian** Key Laboratory of Industrial Microbiology, Tian** Engineering Research Center of Microbial Metabolism and Fermentation Process Control, College of Biotechnology, Tian** University of Science and Technology, Tian**, 300457, People’s Republic of China

    Rui Tang, Yanbing Shen, Min Wang, Haijie Zhou & Yunqiu Zhao

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  1. Rui Tang
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  2. Yanbing Shen
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Correspondence to Yanbing Shen or Min Wang.

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Tang, R., Shen, Y., Wang, M. et al. Highly efficient synthesis of boldenone from androst-4-ene-3,17-dione by Arthrobacter simplex and Pichia pastoris ordered biotransformation. Bioprocess Biosyst Eng 42, 933–940 (2019). https://doi.org/10.1007/s00449-019-02092-y

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