Applied Biochemistry and Biotechnology

, Volume 186, Issue 2, pp 384–399 | Cite as

Co-addition Strategy for Enhancement of Chaetominine from Submerged Fermentation of Aspergillus fumigatus CY018

  • Chang-Qing Liu
  • Zheng-Hua Pan
  • Fa-Liang An
  • Yan-Hua Lu


Chaetominine (CHA), a novel framework tripeptide alkaloid, imparts an attractive cytotoxic against the human leukemia cell line K562, which is produced by Aspergillus fumigatus CY018. However, its pharmacological research is restricted by low yields in submerged culture, which needs to be resolved immediately by biotechnology. In this work, a co-addition strategy was applied to promote CHA production based on related inhibitors’ addition and precursors’ addition, inspired by the biosynthetic pathway analysis of CHA. CHA production reached 53.87 mg/L by addition of 10 mM shikimate, 10 mM anthranilate, 20 mM tryptophan, and 10 mM alanine in shake flask. Compared to the control without addition of precursors, the activity of 3-deoxy-arabino-heptulosonate-7-phospahte (DAHP) synthase was significantly improved and the transcription levels of critical genes in shikimate pathway were up-regulated responded to the co-addition of precursors. The improvement of CHA production by co-addition of precursors was also successfully reproduced in the lab-scale bioreactor (5-L) system, in which CHA production reached 46.10 mg/L. This work demonstrated that precursors’ co-addition was an effective strategy for increasing CHA production, and the information obtained might be useful to the further improvement of CHA on a large scale.


Chaetominine Aspergillus fumigatus Shikimate pathway Co-addition strategy Submerged fermentation 



This work was supported by the National Natural Science Foundation of China (No. 81741156), the Shanghai Sailing Program (17YF1403700), and the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12010_2018_2714_MOESM1_ESM.docx (308 kb)
ESM 1 (DOCX 308 kb)


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Copyright information

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

Authors and Affiliations

  • Chang-Qing Liu
    • 1
  • Zheng-Hua Pan
    • 1
  • Fa-Liang An
    • 1
  • Yan-Hua Lu
    • 1
  1. 1.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiPeople’s Republic of China

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