Improvement of Curvulamine Production by Precursors Co-addition Strategy in Liquid Culture of Marine-Derived Fungus Curvularia sp. IFB-Z10

  • Xing-Chen Wei
  • Chang-Qing Liu
  • Ri-Yu Zhang
  • Gao-Fan Zheng
  • Fa-Liang AnEmail author
  • Yan-Hua LuEmail author


Curvulamine, a novel scaffold alkaloid with remarkable selective antibacterial activity, is produced by marine fungus Curvularia sp. IFB-Z10. However, its deep pharmaceutical research and application are severely restricted by the low yield, which needs to be solved urgently. The purpose of this study was to improve curvulamine production via precursors co-addition strategy and further reveal the regulation mechanism. In this work, the optimal precursors co-addition conditions were firstly obtained, and curvulamine production achieved 166.74 mg/L with the supply of 250 mg/L alanine and 200 mg/L proline at 60 h, which was 4.08 times that of control. It was observed that under alanine and proline stimulation, fungus exhibited the morphology of a small-diameter compact pellet. Furthermore, the organic acid levels in central carbon metabolism (CCM) were declined with precursors supplement. Besides, precursors also induced the critical biosynthetic gene transcriptions. The above findings collectively promoted curvulamine synthesis. Finally, Curvularia sp. IFB-Z10 fermentation process was successfully established by feeding alanine and proline at 0.021 g/L/h and 0.017 g/L/h rate from 60 to 72 h, and curvulamine production reached 133.58 mg/L in a 5-L bioreactor. The information acquired would facilitate the enhancement of curvulamine yield in submerged fermentation and the research on synthesis regulation of other alkaloids.


Curvulamine Curvularia sp. IFB-Z10 Precursors co-addition Morphology Organic acids Biosynthetic genes Submerged fermentation 



This study was funded by the National Natural Science Foundation of China (41876189), the National Key R&D Program of China (2018YFC1706200), the 111 Project (B18022), and the Fundamental Research Funds for the Central Universities (22221818014).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

12010_2019_3072_MOESM1_ESM.docx (487 kb)
ESM 1 (DOCX 487 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiPeople’s Republic of China

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