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Applied Microbiology and Biotechnology

, Volume 72, Issue 3, pp 486–491 | Cite as

Biotransformation of tolbutamide to 4′-hydroxytolbutamide by the fungus Cunninghamella blakesleeana

  • Haihua Huang
  • Xiuwei Yang
  • Qiang Li
  • Lu Sun
  • Dafang ZhongEmail author
Biotechnological Products and Process Engineering

Abstract

The hypoglycemic drug tolbutamide is commonly used as a probe drug to evaluate CYP2C9 enzyme activity in terms of production of 4′-hydroxytolbutamide. In the present study, an initial screening of seven filamentous fungi was carried out to identify which was most competent to transform tolbutamide into 4′-hydroxytolbutamide. From this screening, the fungus Cunninghamella blakesleeana AS 3.910 was selected as a suitable bioconverter. At a concentration of 1.2 mg ml−1, the growing fungus transformed 95.0% of tolbutamide into 4′-hydroxytolbutamide in 96 h. With resting culture, the yield could reach 91.7% and exceeded 91.0% even when the tolbutamide concentration was increased to 4.0 mg ml−1. On scale-up to 3 l buffer containing 12.0 g tolbutamide, 90% of tolbutamide was transformed into 4′-hydroxytolbutamide in 96 h. Work-up of the broth by column chromatography and recrystallization yielded 6.5 g (53.9% recovered) of 4′-hydroxytolbutamide with a purity of more than 99%. These results suggest C. blakesleeana AS 3.910 is a useful biosynthetic tool in the preparation of 4′-hydroxytolbutamide.

Keywords

Nuclear Magnetic Resonance Biotransformation Tolbutamide CYP2C9 Activity Cunninghamella 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgement

This work was supported by Grant 2003AA2Z347C of the 863 Program of China.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Haihua Huang
    • 1
  • Xiuwei Yang
    • 2
  • Qiang Li
    • 2
  • Lu Sun
    • 3
  • Dafang Zhong
    • 1
    Email author
  1. 1.Center for Drug Metabolism ResearchShanghai Institute of Materia Medica, Chinese Academy of SciencesShanghaiPeople’s Republic of China
  2. 2.College of Life ScienceJilin UniversityChangchunPeople’s Republic of China
  3. 3.Laboratory of Drug Metabolism and PharmacokineticsShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China

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