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A highly active pantothenate synthetase from Corynebacterium glutamicum enables the production of d-pantothenic acid with high productivity

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Abstract

d-Pantothenic acid (vitamin B5) has wide applications in the feed, food, chemical, and pharmaceutical industries. Its biological production routes which employ pantothenate synthetase (PS) as the key enzyme are attractive since they avoid the tedious and time-consuming optical resolution process. However, little data is available on the activity and kinetics of this enzyme, hampering the rational selection of an efficient enzyme for the biological production of d-pantothenic acid. In this study, six phylogenetically distant PS-encoding genes, from Escherichia coli, Corynebacterium glutamicum, Bacillus subtilis, Bacillus thuringiensis, Bacillus cereus, and Enterobacter cloacae, were expressed in E. coli. The PS from C. glutamicum exhibited a specific activity of 205.1 U/mg and a turnover number of 127.6 s-1, which to our best knowledge are the highest values ever reported. The addition of substrates (d-pantoic acid and β-alanine) to the E. coli strain harboring this enzyme during the early log phase of fermentation resulted in the production of 97.1 g/L of d-pantothenic acid within 32 h, corresponding to a conversion yield of 99.1% and a productivity of 3.0 g/L/h. To the best of our knowledge, this is the highest productivity reported to date.

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Acknowledgments

This work was supported by the CAS-TWAS President’s Fellowship Program, the Science and Technology Service Network Initiative of CAS (KFJ-SW-STS-164), Youth Innovation Promotion Association of CAS, and the CAS/SAFEA International Partnership Program for Creative Research Teams.

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Author notes

  1. Fitsum Tigu and Junli Zhang contributed equally to this work.

Authors and Affiliations

  1. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, Beijing, 100101, China

    Fitsum Tigu, Junli Zhang, Guoxia Liu, Zhen Cai & Yin Li

  2. University of Chinese Academy of Sciences, Beijing, 100190, China

    Fitsum Tigu & Junli Zhang

Authors
  1. Fitsum Tigu
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  2. Junli Zhang
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  3. Guoxia Liu
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  4. Zhen Cai
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  5. Yin Li
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Corresponding authors

Correspondence to Zhen Cai or Yin Li.

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Tigu, F., Zhang, J., Liu, G. et al. A highly active pantothenate synthetase from Corynebacterium glutamicum enables the production of d-pantothenic acid with high productivity. Appl Microbiol Biotechnol 102, 6039–6046 (2018). https://doi.org/10.1007/s00253-018-9017-2

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  • DOI: https://doi.org/10.1007/s00253-018-9017-2

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