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Metabolic engineering of Bacillus subtilis for biosynthesis of heparosan using heparosan synthase from Pasteurella multocida, PmHS1

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Abstract

Heparosan, the capsular polysaccharide discovered in many pathogenic bacteria, is a promising material for heparin preparation. In this study, the Pasteurella multocida heparosan synthase 1 (PmHS1) module was used to synthesize heparosan with controlled molecular weight, while tuaD/gtaB module or gcaD module was responsible for UDP-precursors production in Bacillus subtilis 168. After metabolic pathway optimization, the yield of heparosan was as high as 237.6 mg/L in strain containing PmHS1 module and tuaD/gtaB module, which indicated that these two modules were key factors in heparosan production. The molecular weight of heparosan varied from 39 to 53 kDa, which indicated that heparosan molecular weight could be adjusted by the amount of PmHS1 and the ratio of two UDP precursors. The results showed that it would be possible to produce safe heparosan with appropriate molecular weight which is useful in heparin production.

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Acknowledgments

This work was financially supported by the Major National Science and Technology Project of China for Significant New Drugs Creation (2012ZX09502001-004), the Innovative Scientific Research Team Fund of Jiangsu Province and PAPD (A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions).

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Xiaofei Chen, Rong Chen, Xiaoxiao Yu, Dongyang Tang, Wenbing Yao & Xiangdong Gao

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  1. Xiaofei Chen
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  2. Rong Chen
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  3. Xiaoxiao Yu
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  4. Dongyang Tang
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  5. Wenbing Yao
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Correspondence to Wenbing Yao or Xiangdong Gao.

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Chen, X., Chen, R., Yu, X. et al. Metabolic engineering of Bacillus subtilis for biosynthesis of heparosan using heparosan synthase from Pasteurella multocida, PmHS1. Bioprocess Biosyst Eng 40, 675–681 (2017). https://doi.org/10.1007/s00449-016-1732-4

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  • DOI: https://doi.org/10.1007/s00449-016-1732-4

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