Integrated Proteomics and Metabolomics Reveal Regulatory Pathways Underlying Quality Differences Between Wild and Cultivated Ophiocordyceps sinensis

Ophiocordyceps sinensis, is an entomopathogenic fungus renowned for its medicinal properties, thriving in the frigid and high-altitude regions of the Qinghai–Tibet plateau. Given the limited availability of wild resources and the increasing recognition of their medicinal value, the cultivation of O. sinensis was initiated. However, there is a paucity of research investigating the disparities in their quality. This study evaluated the primary physiological indicators of both wild and cultivated O. sinensis. It also employed proteome and untargeted metabolome approaches to elucidate the differences in quality and underlying mechanisms between the two types. The results revealed that the contents of key representative components, including polysaccharide, crude protein, adenosine, and mannitol, were higher in wild O. sinensis than in cultivated O. sinensis. A total of 499 differentially expressed proteins (DEPs), including 117 up-regulated and 382 down-regulated DEPs, were identified in wild and cultivated O. sinensis. Additionally, 369 up-regulated differentially accumulated metabolites (DAMs) and 737 down-regulated DAMs were also identified. Wild O. sinensis had higher relative levels of lysophospholipid metabolites, while cultivated O. sinensis had higher relative levels of aldehydes and carboxylic acids. Correlation analysis revealed that different habitats altered 47 pathways shared between the proteome and metabolome, including carbohydrate metabolism and energy metabolism. β-glucosidase and α-galactosidase play essential roles in carbohydrate catabolism and may indirectly influence amino acid synthesis through energy metabolic pathways. The differential expression of polyamine oxidase (PAO) could reflect variations in polyamine metabolism and ammonia production between wild and cultivated O. sinensis. These variations may consequently affect nitrogen homeostasis and the biosynthesis of nitrogen-containing compounds, ultimately leading to differences in nutritional quality. In conclusion, these findings offer a novel perspective on the applications of O. sinensis and serve as a reference for the targeted development of cultivated O. sinensis.