Wang Xin, Li Yin, Li Xiue, Sun Lei, Feng Yetong, Sa Fangping, Ge Yupeng, Yang Shude, Liu Yu, Li Weihuan, Cheng Xianhao
Shandong Key Laboratory of Edible Mushroom Technology, School of Agriculture, Ludong University, Yantai, China.
Yantai Hospital of Traditional Chinese Medicine, Yantai, China.
Front Nutr. 2023 Feb 16;10:1104446. doi: 10.3389/fnut.2023.1104446. eCollection 2023.
Cordycepin, an important active substance in , 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 with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of , and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on 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.
虫草素是冬虫夏草中的一种重要活性物质，具有抗病毒等有益活性。此外，据报道它能有效促进新冠肺炎的综合治疗，因此成为研究热点。已知添加萘乙酸（NAA）可显著提高虫草素产量，但其相关分子机制仍不清楚。我们对不同浓度NAA处理的冬虫夏草进行了初步研究。我们发现，不同浓度NAA处理均抑制了冬虫夏草的生长，且其浓度增加显著提高了虫草素含量。此外，我们对NAA处理的冬虫夏草进行了转录组和代谢组关联分析，以了解NAA处理下虫草素合成的相关代谢途径，并阐明虫草素合成的相关调控网络。加权基因共表达网络分析（WGCNA）、转录组和代谢组关联分析表明，嘌呤代谢途径中编码虫草素合成的基因和代谢产物随NAA浓度变化显著。最后，我们通过分析基因-基因和基因-代谢产物调控网络之间的关系，提出了一条代谢途径，包括虫草素合成关键基因的相互作用；关键代谢产物；嘌呤代谢；三羧酸循环；磷酸戊糖途径；丙氨酸、天冬氨酸和谷氨酸代谢；以及组氨酸代谢。此外，我们发现ABC转运蛋白途径显著富集。已知ABC转运蛋白可转运多种氨基酸，如L-谷氨酸，并参与影响虫草素合成的氨基酸代谢。总之，多个通道共同作用使虫草素产量翻倍，从而为虫草素合成转录与代谢之间的分子网络关系提供重要参考。
