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Extractive fermentation for enhanced production of thailandepsin A from Burkholderia thailandensis E264 using polyaromatic adsorbent resin Diaion HP-20

  • Bing Liu
  • Junyuan Hui
  • Yi-Qiang Cheng
  • Xuehong Zhang
Fermentation, Cell Culture and Bioengineering

Abstract

Thailandepsin A is natural product of Burkholderia thailandensis E264 with potent histone deacetylase inhibitory activities and promising anticancer activities. The titer of thailandepsin A is very low (less than 10 mg/l) from limited empirical fermentation. To facilitate preclinical evaluations and potentially clinical development of thailandepsin A, systematic optimization and extractive fermentation of thailandepsin A from B. thailandensis E264 culture in flasks were investigated in this pilot study. The main fermentation parameters—28°C, pH 7.0, inoculum ratio 1% (v/v), incubation duration 60 h, medium volume 26%, shaking speed 170 rpm, and chloroform as extracting solvent—were determined by single factor experiments. Polyaromatic adsorbent resin Diaion HP-20, when added at a concentration of 4% (w/v), was most effective to reduce feedback inhibition of thailandepsin A and to significantly increase the titer of target product. Central composite design was used to further optimize the fermentation medium for B. thailandensis E264. The optimized medium contains glucose 17.89 g/l, tryptone 34.98 g/l, potassium phosphate 24.84 g/l, and sodium citrate 0.01 g/l, which resulted in a large increase of the titer of thailandepsin A to 236.7 mg/l. Finally kinetic models based on the modified logistic and Luedeking–Piret equations were developed, delivering a good description of temporal variations of biomass, product, and substrate in the fermentation process, which could be used as references for developing large-scale fermentation.

Keywords

Burkholderia thailandensis E264 Central composite design Extractive fermentation Thailandepsin A 

Notes

Acknowledgments

This research was supported by grants from the National Science Foundation of China (NSFC) and 973 Research Programs.

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2012

Authors and Affiliations

  1. 1.State Key Laboratory of Microbial MetabolismSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Biological SciencesUniversity of Wisconsin–MilwaukeeMilwaukeeUSA
  3. 3.Department of Chemistry and BiochemistryUniversity of Wisconsin–MilwaukeeMilwaukeeUSA
  4. 4.ChinAm PharmaTech Wuhan Ltd.WuhanPeople’s Republic of China

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