Multi-omics analysis unravels positive effect of rotenone on the cordycepin biosynthesis in submerged fermentation of Cordyceps militaris

You-Chu Ma; Ping Huang; Xiao-Ling Wang; Gao-Qiang Liu

doi:10.1016/j.biortech.2023.128705

Multi-omics analysis unravels positive effect of rotenone on the cordycepin biosynthesis in submerged fermentation of Cordyceps militaris

Bioresour Technol. 2023 Apr:373:128705. doi: 10.1016/j.biortech.2023.128705. Epub 2023 Feb 4.

Authors

You-Chu Ma¹, Ping Huang², Xiao-Ling Wang¹, Gao-Qiang Liu³

Affiliations

¹ International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology, Changsha, Hunan 410004, China; Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha, Hunan 410004, China; Microbial Variety Creation Center, Hunan Provincial Laboratory of Yuelushan Seed Industry, Changsha 410004, China.
² International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology, Changsha, Hunan 410004, China; Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha, Hunan 410004, China.
³ International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology, Changsha, Hunan 410004, China; Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha, Hunan 410004, China; Microbial Variety Creation Center, Hunan Provincial Laboratory of Yuelushan Seed Industry, Changsha 410004, China. Electronic address: gaoliuedu@csuft.edu.cn.

PMID: 36746212
DOI: 10.1016/j.biortech.2023.128705

Abstract

Cordycepin is the key pharmacologically active compound of Cordyceps militaris, and various fermentation strategies have been developed to increase cordycepin production. This study aimed to investigate the effect of rotenone on cordycepin biosynthesis in submerged fermentation of C. militaris, and also to explore its possible induction mechanisms via multi-omics analysis. Adding 5 mg/L rotenone significantly increased the cordycepin production by 316.09 %, along with mycelial growth inhibition and cell wall destruction. Moreover, transcriptomic analysis and metabolomic analysis revealed the accumulation of cordycepin was promoted by alterations in energy metabolism and amino acid metabolism pathways. Finally, the integration analysis of the two omics confirmed rotenone altered the nucleotide metabolism pathway toward adenosine and up-regulated the cordycepin synthesis genes (cns1-3) to convert adenosine to cordycepin. This work reports, for the first time, rotenone could act as an effective inducer of cordycepin synthesis.

Keywords: Cordycepin biosynthesis; Cordyceps militaris; Multi-omics; Rotenone; Submerged fermentation.

MeSH terms

Adenosine / metabolism
Cordyceps* / metabolism
Deoxyadenosines / metabolism
Fermentation
Multiomics
Rotenone / metabolism
Rotenone / pharmacology

Substances

cordycepin
Rotenone
Deoxyadenosines
Adenosine