Epigenetics as a design variable in heterologous expression.

Modulating DNA methylation in Burkholderia sp. FERM BP-3421 can improve heterologous protein expression by up to 2.4-fold, highlighting epigenetics as a key design variable.

• Why it matters: Current strategies for enhancing heterologous expression focus mainly on DNA sequence modifications, but the role of epigenetic factors like DNA methylation remains largely unexplored, limiting potential improvements in yield.
• What they did: The study involved deleting or overexpressing four predicted DNA methyltransferases in Burkholderia sp. FERM BP-3421, then assessing their effects on the host's transcriptome, metabolome, and heterologous GFP expression with three different promoters.
• The result: Modulating DNA methylation significantly impacted gene expression and metabolite profiles, with context-dependent effects on GFP expression, demonstrating that epigenetics can be harnessed to enhance heterologous production yields.