Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in Cordyceps militaris

Xin Wang; Yin Li; Xiue Li; Lei Sun; Yetong Feng; Fangping Sa; Yupeng Ge; Shude Yang; Yu Liu; Weihuan Li; Xianhao Cheng

doi:10.3389/fnut.2023.1104446

Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in Cordyceps militaris

Front Nutr. 2023 Feb 16:10:1104446. doi: 10.3389/fnut.2023.1104446. eCollection 2023.

Authors

Xin Wang¹, Yin Li², Xiue Li¹, Lei Sun³, Yetong Feng¹, Fangping Sa¹, Yupeng Ge¹, Shude Yang¹, Yu Liu¹, Weihuan Li¹, Xianhao Cheng¹

Affiliations

¹ Shandong Key Laboratory of Edible Mushroom Technology, School of Agriculture, Ludong University, Yantai, China.
² Yantai Hospital of Traditional Chinese Medicine, Yantai, China.
³ College of Plant Protection, Jilin Agricultural University, Changchun, China.

Abstract

Cordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of C. militaris, and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on C. militaris treated with NAA to understand the relevant metabolic pathway of cordycepin synthesis under NAA treatment and elucidate the relevant regulatory network of cordycepin synthesis. Weighted gene co-expression network analysis (WGCNA), transcriptome, and metabolome association analysis revealed that genes and metabolites encoding cordycepin synthesis in the purine metabolic pathway varied significantly with the concentration of NAA. Finally, we proposed a metabolic pathway by analyzing the relationship between gene-gene and gene-metabolite regulatory networks, including the interaction of cordycepin synthesis key genes; key metabolites; purine metabolism; TCA cycle; pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; and histidine metabolism. In addition, we found the ABC transporter pathway to be significantly enriched. The ABC transporters are known to transport numerous amino acids, such as L-glutamate, and participate in the amino acid metabolism that affects the synthesis of cordycepin. Altogether, multiple channels work together to double the cordycepin yield, thereby providing an important reference for the molecular network relationship between the transcription and metabolism of cordycepin synthesis.

Keywords: metabolic pathway; molecular mechanism; naphthalene acetic acid (NAA); regulatory network; transcriptome.

Grants and funding

This research was funded by the Edible Mushroom Genetic Breeding Innovation Team of Shandong Agricultural Industry Technology System, grant number SDAIT-07-03, the Cooperation Project of University and Local Enterprise in Yantai of Shandong Province, grant number 2021XDRHXMPT09, and Traditional Chinese Medicine Science and Technology Project in Shandong Province, grant number M-2022040.