Transcriptomics and metabolomics profiling coumestrol and psoralen synthesis pathways and potential regulators in Inonotus hispidus L-1
Coumestrol and psoralen as important derivatives of coumarins were mainly found in plants and play important roles in anticancer and anti-inflammation but were less reported in fungi.Our study successfully isolated and characterized Inonotus hispidus L-1,a strain with high polysaccharides and flavonoids.Metabolomic analysis indicated that the content of coumestrol and psoralen in basidiomata of I.hispidus L-1 was significantly higher than that in mycelia and primordia.Combining transcriptomics and metabolomics approaches,the synthetic pathways and regulatory genes involved in the production of coumestrol and psoralen were elucidated.The synthesis of coumarin and psoralen in I.hispidus L-1 has a common precursor,L-phenylalanine.L-phenylalanine synthesis was co-regulated by the glycolysis/gluconeogenesis pathway and the phenylalanine pathway,and its levels were significantly elevated in the primordium and basidioma stages.More interestingly,the downstream metabolites in the P-coumarate acid synthesis pathway,by using L-phenylalanine as a precursor,were significantly increased.These downstream metabolites include 2,7,4'-trihydroxyisoflavanone and coumestrol in the isoflavonoid biosynthesis pathway,as well as 7-hydroxycoumarine and psoralen in the coumarin biosynthesis pathway.The synthesis of coumestrol and psoralen was mainly regulated by the phenylalanine ammonia-lyase(APL),APL1,and glutathione S-transferase omega-like 2(ECM4)genes.The results highlight the potential of I.hispidus L-1 as a valuable source of coumarins and psoralens for the development and application of nutraceuticals.