Bioprocess and Biosystems Engineering

, Volume 42, Issue 5, pp 753–761 | Cite as

Improvement of kojic acid production in Aspergillus oryzae AR-47 mutant strain by combined mutagenesis

  • Weimeng Feng
  • Jinrui Liang
  • Bingbing Wang
  • Jianhua ChenEmail author
Research Paper


Kojic acid is a kind of secondary metabolites, whose biosynthesis pathway remains unclear to date. It is produced industrially by microbial fermentation, and thus, mutagenesis breeding still plays a vital role for obtaining strains with high kojic acid production. The starting strain KA-11 isolated from mildewed fruits was identified as Aspergillus oryzae and then subjected to a combined mutagenesis program including microwave mutagenesis, UV irradiation, heat-LiCl, atmospheric, and room temperature plasma (ARTP). The kojic acid production was increased by 47.0%, 87.1%, 126.2%, and 292.3% compared with the starting strain KA-11 after each mutagenesis stage. A mutant strain AR-47 with kojic acid production of 96.5 g/L in flask-shake fermentation was finally obtained. The fermentation time also decreased from 7 to 5 days. Real-time quantitative PCR was used to determine the transcriptional expression levels of genes that may be relevant to kojic acid biosynthesis, including kojA, kojR, kojT, AO090113000141, AO090113000143, AO090113000145, nrtA, and laeA. The results showed that the transcriptional expression levels of all these genes in high yield strain AR-47 had increased compared with the starting strain KA-11.


Aspergillus oryzae Atmospheric and room-temperature plasma (ARTP) Combined mutagenesis Kojic acid production Real-time quantitative PCR Transcriptional expression 



This study was supported by “111 Project” from the Ministry of Education of China and State Administration of Foreign Experts Affairs of China (no. 111-2-07) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Compliance with ethical standards

Conflict of interest

We declare no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Weimeng Feng
    • 1
  • Jinrui Liang
    • 1
  • Bingbing Wang
    • 1
  • Jianhua Chen
    • 1
    Email author
  1. 1.School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina

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