Applied Biochemistry and Biotechnology

, Volume 187, Issue 4, pp 1502–1514 | Cite as

Enhancement of Bacitracin Production by NADPH Generation via Overexpressing Glucose-6-Phosphate Dehydrogenase Zwf in Bacillus licheniformis

  • Shan Zhu
  • Dongbo Cai
  • Ziwei Liu
  • Bowen Zhang
  • Junhui Li
  • Shouwen ChenEmail author
  • Xin MaEmail author


Bacitracin, a kind of cyclic peptide antibiotic mainly produced by Bacillus, has wide ranges of applications. NADPH generation plays an important role in amino acid synthesis, which might influence precursor amino acid supply for bacitracin production. In this study, we want to improve bacitracin yield by enhancing intracellular precursor amino acids via strengthening NAPDH generation pathways in the bacitracin industrial production strain Bacillus licheniformis DW2. Based on our results, strengthening of NADPH pathway genes (zwf, gnd, ppnk, pntAB, and udhA) could all improve bacitracin yields in DW2, and the glucose-6-phosphate dehydrogenase Zwf overexpression strain DW2::Zwf displayed the best performance, the yield of which (886.43 U/mL) was increased by 12.43% compared to DW2 (788.40 U/mL). Then, the zwf transcriptional level and Zwf activity of DW2::Zwf were increased by 12.24-fold and 1.57-fold; NADPH and NADPH/NADH were enhanced by 61.24% and 90.63%, compared with those of DW2, respectively. Moreover, the concentrations of intracellular precursor amino acids (isoleucine, leucine, cysteine, ornithine, lysine, glutamic acid) were all enhanced obviously for bacitracin production in DW2::Zwf. Collectively, this research constructed a promising B. licheniformis strain for industrial production of bacitracin, more importantly, which revealed that strengthening of NADPH generation is an efficient strategy to improve precursor amino acid supplies for bacitracin production.


Bacillus licheniformis NADPH generation Bacitracin Glucose-6-phosphate dehydrogenase Zwf Precursor amino acid 


Author’s Contribution

D Cai and S Chen designed the study. S Zhu, D Cai, and Z Liu carried out the molecular biology studies and construction of engineering strains. S Zhu, Z Liu, B Zhang, and J Li carried out the fermentation studies. S Zhu, D Cai, S Chen, and X Ma analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.

Funding Information

This work was supported by the Technical Innovation Special Fund of Hubei Province (2018ACA149) and the Science and Technology Program of Wuhan (20160201010086).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12010_2018_2894_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Environmental Microbial Technology Center of Hubei Province, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life SciencesHubei UniversityWuhanPeople’s Republic of China
  2. 2.Lifecome Biochemistry Co. Ltd.NanpingPeople’s Republic of China

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