How DNA Methylation Regulates Plant Natural Product Biosynthesis: From Epigenetics to Secondary Metabolism

Plants produce a wide array of secondary metabolites, also known as natural products (NPs), with diverse chemical properties. These compounds play crucial roles in plant development and defence against environmental stress. DNA methylation has emerged as a key regulator of secondary metabolism by modulating gene expression at the transcriptional level. By providing a new source of variation, DNA methylation holds great potential for enhancing NP accumulation, offering valuable insights for scientists and breeders alike. However, our understanding of current research trends in this area is limited. In this respect, we summarise the most recent findings on the roles of DNA methylation in the biosynthesis of three major classes of important NPs—pigments, flavour compounds and medicinal substances, including methylating and demethylating enzymes, the global methylation dynamics and the dual regulation of DNA methylation in different genomic regions or sequence contexts on gene expression. We also discuss alternative splicing regulated by DNA methylation in plants. Finally, we highlight key unanswered questions and propose potential future research directions to further unravel the regulatory mechanisms of DNA methylation in NP biosynthesis. This knowledge will facilitate the development of innovative strategies for improving plant quality and increasing NP production.