Improved production of jiangxienone in submerged fermentation of Cordyceps jiangxiensis under nitrogen deficiency

Bioprocess Biosyst Eng. 2018 Oct;41(10):1417-1423. doi: 10.1007/s00449-018-1970-8. Epub 2018 Jun 14.

Abstract

Jiangxienone produced by Cordyceps jiangxiensis exhibits significant cytotoxicity and good selectivity against various human cancer cells, especially gastric cancer cells. In this work, the effect of nitrogen deficiency on the accumulation of jiangxienone and the transcription levels of jiangxienone biosynthesis genes was studied in submerged fermentation of C. jiangxiensis. Results showed that accumulation of jiangxienone was improved under nitrogen deficiency condition. A maximal jiangxienone content of 3.2 µg/g cell dry weight was reached at 5 mM glutamine, and it was about 8.9-fold higher than that obtained at 60 mM glutamine (control). The transcription levels of the biosynthetic pathway genes hmgr and sqs and the nitrogen regulatory gene areA were upregulated by 7-, 14-, and 28-fold, respectively, in culture with 5 mM glutamine compared to the control. It was hypothesized that the jiangxienone biosynthesis may involve the mevalonate pathway in C. jiangxiensis. Taken together, our study indicated that nitrogen deficiency is an efficient strategy for enhancing jiangxienone accumulation in submerged fermentation of C. jiangxiensis, which is useful for further understanding the regulation of jiangxienone biosynthesis.

Keywords: Biosynthetic gene; Cordyceps jiangxiensis; Jiangxienone; Nitrogen deficiency.

MeSH terms

  • Cordyceps / growth & development*
  • Cyclohexanones / metabolism*
  • Fungal Proteins / biosynthesis
  • Fungal Proteins / genetics
  • Gene Expression Regulation, Fungal / physiology
  • Indans / metabolism*
  • Nitrogen / deficiency*

Substances

  • Cyclohexanones
  • Fungal Proteins
  • Indans
  • jiangxienone
  • Nitrogen