Silymarin is the main phytochemical extracted from Silybum marianum (L.) Gaertn. fruits. It is principally composed of six flavonolignans, which can be present in different relative proportions in the distinct S. marianum chemotypes. Few and sometimes contradictory information is available both about silymarin biosynthesis and how the different chemotypes can arise. According to the commonly accepted pathway, the occurrence of random radical coupling of the two flavonolignan precursors is the main driver of chemotype differentiation. In this work we studied two contrasting S. marianum chemotypes at biochemical, genetic, and transcriptional level. By analysing the flavonolignan accumulation process during fruit ripening and the chemotype segregation ratio after crossing, we concluded that S. marianum chemotype differentiation is a metabolically regulated process driven by a monogenic hereditable factor involved in silydianin biosynthesis. Transcriptome sequencing of the fruit shell during active silymarin accumulation revealed that dirigent-like transcripts putatively involved in the selective radical coupling...

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